Clinical Trials For Colon Cancer

>> this program is made possible in part through a grant provided by the national sponsors of cancer: emperor of all maladies, coordinated through weta public television. wvpt and the uva cancer center present "cancer: defeating the emperor."

learn how researchers and physicians are battling mankind's most fearsome malady, utilizing the latest in cutting-edge technologies, through clinical trials, nanotechnology and targeted treatments. it's a new age in the fight

against cancer, and unlocking a cure maybe closer than we think. >> good evening, everyone. my name is dr. tom loughran. i'm the director of the uva cancer center. i'd like to thank you all tonight for joining us for a special educational series,

cancer: defeating the emperor. since the introduction of chemotherapy in the 1940's, we've made great strides in cancer therapy. we now know much better why cancer starts and develops. we are using that knowledge to develop better therapy.

there's still a lot of work to be done. however, we're really at an inflection point in the history of cancer care and cancer treatment. ten years from now, the landscape of cancer treatment is going to be vastly different.

as a researcher and a physician myself, i've never been more excited about the future of cancer care and cancer research than i am now. and that's important, because behind every cancer statistic, there's a father, a mother, a brother, a sister, or a friend.

this knowledge drives our work. as a national cancer institute-designated center, uva is only one of sixty-eight centers nationwide, continuously seeking out new therapy and knowledge for developing better therapy through research and clinical trials.

at the end of the day, it comes down to people helping people. for my colleagues and myself, this is so much more than a job. tonight, you'll meet three exceptionally, outstanding, internationally-known uva researchers whose research right now is leading to better

treatment possibilities for the people in our community as well as across the country. thank you for being a part of this special evening. and particularly, thank you for your continued support of the uva cancer center. i want to give special thanks to

our partner, wvpt, for making this evening possible. now, it's my distinct pleasure to turn over the rest of the ceremony to larry sabato, our host for the evening. larry, take it away. thank you. >> thank you so much.

dr. loughran, thank you very much, and i am so pleased to be here with you tonight. i can't imagine there's a more important event going on in this entire area, because, after all, all of us directly or indirectly are affected by cancer. we've experienced it ourselves,

in our family, in our circle of friends. it doesn't take very long in life to realize how important it is. and the uva cancer center has been doing such as a wonderful job for many years, and i think it's accelerated over the years.

the new techniques and technologies that you're going to hear about tonight caused me to say that the u -- we ought to rename the uva cancer center "the center for hope" because there is a lot of hope in a field that once had very little. i remember when i was growing up

in the 50s and 60s, you didn't even want to use the name cancer, you remember? you might refer to it as the "c-word." well, it's time to adopt a new c-word, and the c-word is "cure." and it's been a long time

coming. many of us here in this auditorium remember when president nixon, in 1971, declared war on cancer. and a lot of money was appropriated for that time. we were still living with the euphoria of the moon landing,

and we managed to do this within a decade. and there was a lot of talk about how we could cure cancer in a decade. unfortunately, everybody discovered that it was much more complicated than anybody thought.

so, treatments may be more important than cures. but we're well on our way because of some of the researchers that you're going to meet tonight. they're just terrific people, and it's an honor to be with them and have a chance to see

what they're doing in the laboratory and with patients. i mentioned that all of us have experiences with cancer, in my own family. my dear old dad, who passed away 20 years ago last week, unfortunately had pancreatic cancer, which was one of the

most deadly forms of cancer. and it certainly was at the time he got it, which was the early 1990's. and by the time they figured out what he had, he only had three months left. that's how bad things were in those days.

well, already, tremendous progress has been made. and because so many members of my family ended up having pancreatic cancer, i now undergo screenings -- regular screenings at the cancer center myself with a great team that reid adams and others have put together there.

so, i understand a bit of what some of you have gone through. i understand a bit of why we need to be as concerned as i know we all are about this important topic. so, without any delay, any further delay, i want to bring out our first researcher, dr.

kim kelly. kim is an associate professor of biomedical engineering and resident faculty of the robert m. berne cardiovascular research center at uva. her work focuses on the development of technology for the early detection of cancer

and the targeted delivery of cancer drugs to improve patient prognosis. dr. kelly is a member of snm, the american pancreatic association, and the aacr. she was named a william guy forbeck scholar in 2005 and awarded an aacr pancreatic

cancer action network career development award in 2007. additionally, kim has more than 30-peer reviewed and invited publications and has served as a reviewer for numerous journals. she's also a delightful person. please welcome, dr. kim kelly. >> thank you, larry.

>> thank you. >> when i was a graduate student, i discovered i was really good at identifying differences between things, so, really being able to figure out what made a cancer cell unique and how to bring things to it. and so, when i was looking for a

project or a disease that would really benefit from that, pancreatic cancer stood out as one that was really in desperate need of early detection and then new targeted therapies. and then, through the work that i've done with different agencies like pancreatic cancer

action network, i've really got to meet lots of advocates and survivors and their families. and it's really reinforced why i got into this. it's a great group of people and it's unfortunate that they've had to deal with this disease. so i want to talk to you a

little bit today about what we're doing for pancreatic cancer. and so, here's what you typically see when you go on websites, all of those things, you usually see the statistics, right? here's some lines and some

graphs, and it brings you back to second grade when you were first learning how to graph and do lines. but people are just not statistics. everybody is very individual. so how many of you guys out here tonight have been touched by

cancer, either are a survivor yourself or are -- have family members that are survivors? yeah, unfortunately, quite a few of you. and you all know that it is a devastating disease. and so, strides have been made for different cancers, for

example prostate and such, but it hasn't been the case for pancreatic cancer. and i'll talk to you about our efforts in pancreatic cancer for a little bit. but there's been a shift in how clinicians and how researchers are looking at cancer.

it is not just a statistic. everybody is an individual. and with that being said, everybody's tumor is very different. and so, we are starting to look at this and we're calling it "precision medicine," the ability to use the patient's

dna, proteins, rna, things that are unique to the cancer and to the patient's cancer to design treatment that will go directly to the tumor and hopefully cut out on the side effects. so if you guys have known people or have been survivors yourself, you know that some of the drugs

that are used currently for cancer treatment have pretty harsh side effects. there's hair loss, typically, nausea, vomiting, and other things that are there. what we want to do is we want to deliver more of the drug to the tumor so we can kill it without

giving the side effects. what we also want to do with imaging, and i'll show you this in a little bit, is to be able to tell, "ok, detect the tumors earlier." the earlier you find a tumor, the better the chance of the patient prognosis, the better

chance you have of surviving. we also want to be able to tell with imaging what drug you should take, if you are taking a drug that doesn't work, that doesn't work at six weeks or however many weeks that you are not taking the correct drug for you.

so precision medicine is where we want to go. so again, let's go back to these cancer trends. so again, everybody's not a statistic, but what i want to alert you to is that there has been great strides, there's a lot of knowledge that has been

gained over the 40 years since the war on cancer was declared. and there are a lot of researchers and companies that have taken advantage of this knowledge, which is great news. prostate cancer rates, 99.9% of people survive their diagnosis of prostate cancer.

now, one person dying of cancer is one too many. so we are not happy with those kind of rates, but they're much better than they were back 40 years ago when cancer was a deadly word. and in fact, my grandparents are of the generation where they

wouldn't -- won't even go and get a colonoscopy because they're so afraid that they will have cancer and they're still of that timeframe where there was nothing that could be done about it. so i have been talking to my family for a long time about the

importance of screening. but there's certain cancers like lung and pancreatic cancer where the prognosis hasn't changed in 40 years. and that's because there isn't ways to do early detection. for the mammogram or for breast cancer, there's mammogram.

for prostate cancer, there's psa and the digital rectal exam. colonoscopy has revolutionized how colon cancer is detected and treated. there are no ways to do this for colon and pancreatic cancer. and in fact, it's so dire that pancreatic cancer and lung

cancer -- or pancreatic cancer is set to become the number two leading cause of death in the us due to cancer by 2030. that's not good. so we in my lab and other researchers across the country are focusing on ways to do early detection, and then do this

precision medicine where we can then go ahead and give the clinicians the tools to be able to treat the tumor. so how do we do this? we do this by playing with viruses. and so, bacterium have viruses that only will bind to them.

so we've gone in and we can modify them. so they will -- they will put something here that are like keys. and we can go ahead and screen these keys for individual locks on a tumor cell. and so, that means that we are

identifying a lock that is specific for the tumor cell and not anywhere else in the body. it will just be on the tumor cell. we can develop things that will go directly to the tumor and nowhere else. and we're doing that in the lab

right now. we currently have a clinical trial for this in pancreatic we use these viruses, we screen for them, we identify this lock. and in the process, we identify the key. so it becomes a really great tool for doing what it is that

we want to do. one of these is imaging. and the reason why you want to image the pancreas or pancreatic cancer, again, early detection is much better. the earlier you can get it before the cancer starts to invade or metastasize, the much

better it is for the patient. but look where the pancreas is. there's the stomach, the liver, in the back, there are the kidneys. it's in the middle of the body. the other problem with the pancreas is that it doesn't like to be poked.

it gets really irritated if it's poked. so, the pancreas has two functions. it allows you to digest all of your protein, so it puts enzymes into your small intestine. but it also controls insulin. so if you poke the pancreas, you

can release some of those digestive enzymes which go ahead and start eating the pancreas and you can get this disease called chronic pancreatitis. so it's not like other areas of the body where you can just go in and do a biopsy. it's like, oh, we see, you know,

a clinician will see something on a conventional image, like a ct or mr. let's go in and biopsy it and see what happens. it doesn't -- the pancreas really doesn't like that so much. and the other thing about

pancreatic cancer is it will start to metastasize under a centimeter. so we have to detect it when it's the size of an m&m, the size of an m&m hidden in the middle of the body. and ct or cat scans and mri really are not good at doing

this. and in fact, there has been several papers written and published in scientific journals where patients will actually be screened for pancreatic cancer because they have a family history. it'll be negative, negative, and

then six months later, a patient could present with a surgically-unresectable pancreatic tumor, and surgery's the only cure for pancreatic cancer, and then, within three months, unfortunately, succumb to their illness. so it is vitally important that

we detect this and we can detect it very small. so, the way to do this is to make the tumor light up. so we can take that key that we found to the lock that's on that tumor and we can put an agent in it that will allow the clinicians or the radiologist to

see it. and we can inject it into a person. and in fact, we have a clinical trial going on right here at uva to do this. and honestly, it really takes a village. so with the support of the

cancer center and other colleagues like todd bauer and reid adams who are surgeons, and sandra burks, brigitte kelly. so, anyway, what i'm saying is that it really does take a village to get these things from the bench, from the laboratory bench all the way to the clinic.

but uva has found a way to do this and it's supporting this really great research. but what we've been able to do is inject it into a human, and then, it will light up the tumor. these are tumors. the rest of this is the normal

pancreas. so the surgeon can go ahead and remove those tumors and they can start detecting them, hopefully, if the clinical trials work, much, much earlier when the -- when the tumors are curable. so that's the hope, early detection.

but also what we can do, and dr. kester, when he comes out, will talk about this more. but we can start using things, nanotechnology. so, it's so small. it's one twenty thousandth the width of a human hair. these are little materials that

have different properties when they're so small. and what we can do is we can take some of the drugs that have the terrible side effects that make the nausea and the vomiting and the hair loss -- we can put them in the middle of these little nanoparticles inside, and

on the outside, we can put our so that way they're protected as they're going through the bloodstream. they don't see any other cell, not like a conventional chemotherapeutic that goes into every cell in the body which is why you have the side effects.

and these will be delivered directly to the tumor where they fit into the lock, they are recognized as being home, they go inside and they can release their chemotherapeutic. and that's where they can kill the tumor cells specifically. again, this is precision

medicine, being able to find this key and this lock on patients' tumors. so, finally, i just want to leave this with what keeps me going, talking to patients in why we are doing this. so we're doing all of this research, and it's really

excited -- exciting, and i'm incredibly passionate about it. but it's really so we can have more birthdays with our family and our friends, more holidays. these are my four daughters. more family vacations where we make them pose ridiculously in egg-shaped things in the new

york zoo. and then, finally, more sporting events where we can go and be excited about what they're -- what they're doing and -- so this daughter just got placed in the state. and so, now, she's representing for junior in the regionals.

but, you know, that's basically what we are excited about in what we're doing. and i'm excited to take your questions when we all get back together on this stage and start talking. so, thank you for this, and i hope this is a start of a

wonderful conversation. i'm always happy to come by and talk, have people in the lab, or to answer anybody's email. so, thank you very much for your attention, and i want to thank uva and the cancer center for supporting the work and for the whole community for being just

so incredibly supported and -- supportive and exciting. so, thank you. >> kim, thank you so much. i told you you would enjoy the presentation for lots of different reasons. but that was just marvelous. and it just tells you the

enormous advances being made and they're being made right here at the university of virginia we can all be proud of that. i know -- kim, i want you to know in just listening to you and thinking about how many people can be saved and how many lives extended, i feel better

already. thank you so much. and now, we're going to continue the good news with dr. robert dreicer. he's the new deputy director and associate director for clinical research at the uva cancer center.

he's a urologic medical oncologist whose clinical practice and research interest are focused on the development of new therapies for patients with cancers of the prostate, kidney, bladder, and testes. joining uva from the cleveland clinic, distinguished

institution, dreicer brings over 25 years of clinical and research experience to the cancer center with the goal of expanding the depth and reach of clinical trials in virginia. we're so lucky to have him at the university of virginia. dr. dreicer.

>> the change in how we understand cancer and how we take care of patients has been revolutionized during my own career when i finished my training in the late 1980's. medical oncology had already been in existence for a couple of decades, but for most

patients with advance cancers of most of the common types, we had very limited therapies to offer. the science has evolved so drastically that our ability as individual practitioners to maintain competency across the spectrum of cancers has become incredibly challenged.

i'm a urologic medical oncologist, and that means taking care of prostate and bladder, kidney, testes cancers, even that has become challenging. but the depth of our understanding, our ability to intervene in many of the major

cancers has changed dramatically, and will continue to change over the next 10 to 20 years, probably to even a greater extent. so, good evening, and we appreciate you coming out. cancer in a group like this, impacts on cancer survivors,

impacts on folks who have friends and family, if it's a personal thing for you, you think about cancer in a very different way. as an academic medical oncologist, i've been in the business a long time. and although i may not be older

than dirt, i'm a grizzled veteran of the work. what i want to try to do is give you a perspective of where things have gone in terms of an academic career. so, over a period of 25 to 30 years, where have we started from, where are we going to and

where are we going to get to? 1973, so medical oncology as a discipline started in 1973 when it was recognized as a medical specialty. if you look at 1989, that's when i started as a junior faculty member at the university of iowa.

so i was trained in an environment. in 1989, those three cancers were cancers, when they metastasize or spread, could be treated and some improvement in the survival of the patient could be seen. that means the major cancers,

lung, colorectal, prostate, breast cancers, when they metastasize in that era, essentially, although we could treat patients, we have very little impact on the natural history of the disease. so let's fast forward and figure out what's happened.

so, period of the 70's, looking at the survival for all cancers, it's about 50%five-year survival. and you fast forward, today, it's about 68%. these are the most common cancers in terms of their survival rates in that

timeframe. and today, again, already, much for those of you who like graphs, the numbers and the line is heading in the right direction. and this is annualized from 1970 through 2005. these are the major cancers,

both lung cancer in men and women, colorectal cancers in men and women, and prostate and bladder cancers, excuse me, and breast cancers. and as you can see, in respect of the age groups, the trends are all heading in the right direction in terms of survival.

i think this is actually a pretty important slide. if you look at the bottom, what it basically tells us is that the decrease in all cancer death rates have resulted in survivals of half a million people. so, this is not just curves, this impacts on people walking

around today. so why did we make such progress? well, to be honest with you, one of the leading reasons why the death rates in the united states from cancer has declined is because of the decrease in tobacco use.

and that cannot be overemphasized in terms of its critical importance. early detection of some cancers has demonstrated the ability to find disease early and to treat it prior to it spreading. an improvement in therapeutics. now, in 197 -- in 1979, in 1989,

the ability to treat many of the cancers that we take care of today was frankly very limited. when i finished my training as a newly minted oncology fellow, i knew basically everything there was to know in medical oncology. i'm not that smart. it was because there was very

limited information. you could take care of a patient with advanced lung cancer, and you could learn all there was to know in terms of the actual therapeutics in a very short period of time. much of what we did was to try to support patients as opposed

to treat them. you fast forward today, lung cancer as a medical discipline is so complex that a general medical oncologist can't be an expert anymore because of the complexity. but therapeutics, in terms of impacting on survival is now

just beginning to be an issue. so, for much of the last 25 years, much of the improvement on survival came here. this is a list of it looks at drug discovery on fda-approved drugs in oncology. so, if you track the line from the 70s and 80s, and you can see

that there was modest improvement, but over the last decade, there has been an extreme change in our ability to develop new therapeutics and get them into the clinics so that we can use these agents. so, how did those drugs get approved?

those drugs got approved because they were entered into patient-based clinical research. when i was a young oncologist, there were more patients and investigators than drugs to study. my first year as a junior faculty member, if i was lucky,

i got to participate in a single trial in all the diseases that i care for with a novel agent. you fast forward today, there are actually not enough patients, centers, and physicians to actually do all the clinical trials that we actually should do to develop

new therapeutics. and that sounds like a bad thing. it's actually a really good challenge to have because it means that progress has been made. our colleagues in pediatric cancer have always done a better

job. pediatric cancer clinical trial accrual rate has always been enormously high. unfortunately, in the adult side, we've not mirrored that. let me give you an anecdote. phase one studies are early human clinical trials.

we have a drug or drugs that have been developed in animal models and tested for safety and are now entering into human-based trials. phase one trials essentially were not just the end of the line but the likelihood that we would see any benefit to the

patient was essentially zero. phase one trials are actually designed to find the appropriate dose and the schedule of the drug that can then be further tested in disease-specific trials. but in 2015, because of the change in drug development, it

is not unusual to actually see significant response rates in phase one trials. that's a major sea change in how we take care of patients. so let me just spend the last couple of minutes and talk about a disease that i take care of all the time and give you a

perspective. so in 1989, metastatic prostate cancer, when a patient walked in the door, we treated them with standard hormonal therapy. and we told them that their survival was limited to about two, two-and-a-half years. because once they progressed

despite our initial therapy, we frankly had no additional therapy. let me show you what clinical trials can do. this is a clinical trial that has been conducted within what's called the national clinical trials network.

that's basically where your tax dollar support the national cancer institute to do clinical and this was a trial that originated out of the eastern cooperative oncology group, a group that i have been a member since my earliest days. and basically what this study

did was it took that same patient with metastatic prostate cancer and randomized the patient to receive the standard treatment that we've used for a long time, plus the same treatment, and in addition, a chemotherapy drug that had been fda-approved for advanced

prostate cancer, and asked a simple question, does a drug that is used later in the disease course when moved up earlier improve outcome? survival was the endpoint. this is the survival curve. this is a kaplan-meier curve. and let me interpret it for you.

you can actually just look up and look at the difference where it says adt alone, 44 months survival, and with the addition of chemotherapy, 57.6 months of that, frankly, is astonishing. many of the drugs that we get approved today improve survival on a median of two, three, or

four months. that means half the folks live three to four months longer. if you look a subset of the patients, the majority of patients in this study, there was a 17-month median improvement in survival. that, frankly, is

mind-shattering for somebody who has been doing this for a long time. this makes an enormous difference in how we take care of patients. this has now become the standard of care, based on a randomized clinical trial, the patients and

their families were willing to participate in. so we're falling short on the adult side. only 3% to 5% of adult patients enter cancer clinical trials. that number is dramatically higher in the pediatric cancer population.

nearly 80% of national cancer institute-sponsored trials, that n is the number of trials, did not achieve either the number of patients needed to complete the trial or do it in the timeline that was originally projected. and 37% of the trials basically didn't complete because they

were not fully accrued. so we learned very little from those studies. so why do cancer clinical trials matter? well, there's been unequivocal palpable progress within my clinical career. i can tell you that it's almost

like waking up after a 30-year sleep when i walk into clinic and understand the tools that i have and the progress that is on the cusp. you know, we've been talking about progress in the cancer wars for a long time. i can tell you from somebody who

has been around taking care of patients when what i could do was really limited to the point is that i can see before the end of my career, and i have a daughter who's going to graduate medical school next month who may wind up being a cancer doc, but by the time i retire, the

progress that we make between now and then will probably be astronomically more than the 30-year period from the time i finished my training until today. and that's because stuff is happening. the science is now catching up

to the clinical progress and has been integrated. but not all of the answers are inherently obvious. that trial that i just showed you, i'm a co-author of that paper, and i was sitting that the table when it was designed. and i can tell you that i

thought that trial had no chance to be positive. the corollary to that is if i knew all the answers, i would be at the racetrack at the moment. that's why we do clinical clinical trials test questions that we don't always understand the answer to.

and even if we're smart, we can't understand things until we test the concept. keep at it. >> ok. thanks. dr. dreicer, thank you so much. and again, i think we were given a large dose of hope, and it was

exciting to hear it. and again, we're lucky to have someone of dr. dreicer's caliber here at the uva cancer center. this is not a telefund, by the way. although, in some respects, i wish it were, but i do want to mention one thing to you before

we bring out our last presenter. i think it's very important that all of us participate in one way or another. and some who have the means should be contributing substantially. and that means a checkbook, of course.

i can -- i can tell you one thing, our friend, debbie ryan, i think many of you know debbie ryan or certainly have heard of her, our long-time uva basket -- women's basketball coach. and debbie developed pancreatic cancer back at the turn of the

century. well, not only is she still with us, she's going a mile a minute. she's a -- she's a complete, and total, and active survivor. and she's very dedicated to the and i just want to warn you, if you see her coming, just give up.

just pull out your checkbook. she did it to me recently. and she has a wonderful technique. she will not leave your office until you give exactly what she wants you to give. but i'm quite serious when i say all of us have friends of means,

some more than others. and i think it's important to approach them and ask them for support. so much progress is being made, but even more progress could be made if more people were giving in a substantial way. we can't depend on the federal

government anymore. we can't depend on the state government anymore for lots of good reasons, some bad ones, some good, but the money is just not there. and a lot of it has to come from us. it has to be private donations.

so, with that pitch, this not being a telethon, let me bring out our third presenter. he's a wonderful guy. dr. mark kester, joined the university of virginia in 2014 as director of the university's institute for nanoscale and quantum scientific and

technological advanced research. what a mouthful, but there's a great acronym, nanostar. his research interests include the design, characterization, and validation of nanotechnologies for targeted cancer drug delivery. by coding microscopic amounts of

drugs or molecular agents in non-toxic wrappers, treatments that would generally be harmful or even deadly to a patient are administered safely exactly where they're needed. dr. kester is co-author of integrated pharmacology, which has been recognized as a highly

commended textbook by the british medical society. please join me in welcoming dr. kester. >> thanks, larry. it's all about legacy. what we do here at uva and what we do here in my lab, this is exciting, groundbreaking

science. and we're truly translating it from the bench to the bedside. we're taking nanotechnology really, really small particles, so small that below the wavelength of light, you can't even see them. we can deliver a million billion

of these particles and each one has a chemotherapeutic targeted to a cancer cell. think of these as little fedex trucks designed to deliver on time all the time only to the what excites me is taking this technology and working with material scientists, engineers,

physicists, chemists, applied mathematicians, and then coming up with the right drug to go in this nanotechnology and then taking it to the clinic. that's the legacy, that's the excitement. that's what's happening right now, right here at university of

virginia. all righty. first two shameless plugs, number one, i am director of the technologically advanced research. wasn't my name, there's a q in it, it has nothing to do with nanostar.

but we are the cross grounds institute that truly integrates faculty from the school of engineering, college of arts and sciences, school of medicine, darden school of business, curry school of education, and the school of architecture. yes, who knew there's

nanoconcrete? hundred faculty members working together to transform electronics, think of your batteries for the vault. excuse me, electronics, better computer chips, energy, batteries for the vault, and in which case, we'll talk about

tonight, medicine. second thing, i want to do the conflict of interest first. some of the technologies i'll be talking about today have been licensed by penn state research foundation to companies i've started, founded and served as officer of, and we'll be talking

about some of those technologies but that's how we get things to the clinic. ok. the reason i chose this is not because i love the words of aaron sorkin, which i do. the reason i talk about this is that about eight, nine years

ago, our group was working on , guess what? these sti's, these signal transduction inhibitors. and surprisingly, the ones we're working on are sphingosine kinase inhibitors. yes, i was scooped for about 20 million people.

and in fact, with tom loughran, the director of the cancer center here at uva, we have in 2013, we're lucky enough to get the only program project, it's a $10 million grant using expertise from uva, penn state, john wayne cancer center, and memorial sloan kettering in new

york to look at multiple drugs that we're developing, including nanotechnology, to treat acute myeloid leukemia where basically we haven't had new therapy in 40 years. one of those programs in that program project is the sphingosine kinase inhibitor.

now what we learned from those studies is it's a great drug, but we want to say even more exciting. sphingosine kinase inhibitors actually stop a pathway of lipid metabolism and it builds up a lipid. it's called ceramide.

ceramide is a lipid that selectively kills cancer cells. you give it to normal cells, they go to sleep. you give it to cancer cells, they die. that's the selectivity we really want in a drug. here's the problem, it's a

lipid, it's a fat. it makes a nice salad dressing, but it's not a therapy. how do you actually take something that's so -- the word is hydrophobic, but it's impermeable, it precipitates, it's toxic. how do you take something that's

so nasty and make it into a drug? the answer is nanotechnology. and that's what we'll spend the next five minutes talking about. so let's do a little nano 101, yes, the future of medicine is small, yeah, it's real small. so just give you some numbers,

the national nanotechnology initiative united states for the last 10 years, spent $3 billion annually on nanotechnology. that's everything from nanoenergy to nanoelectronics to nanographite, which basically -- this is a tennis racket to the head, nano, who knew i play with

nano. basically, we're spending three -- $3 billion annually, and that's not considering what russia, asia, and europe is spending. and some of that money goes to nanomedicine. what we're talking about, kim

kelly talked about at 120,000 the size of the human hair. well, that seems small to me, but really how small? it's so small you cannot see the light that's shining in my eyes right now, it's about 400 to 500 nanometers wavelength. we're going to be talking about

materials that are about 30, 40, 50 nanometers in size. so small it's below the wavelength of light. it's smaller than light. and you got to use electron microscopy and other techniques to actually see these materials. and in fact, you were about 30

times bigger than a glucose molecule. and going from this side, i play tennis, two orders of magnitude below tennis balls a period, two orders of magnitude below that cancer cell, bacteria, virus. somewhere between antibio and a virus is where we have our

nanos. and we'll be talking about nanojackets today and nanoliposomes. but basically, we can put a million billion particles together in one little drop. that's a lot of drug we can put inside our nanotechnology.

so let me describe what we did with the ceramide nanoliposome. and because we're talking about debbie ryan, i'll use a basketball. so we created something called a nanoliposome. so think of this basketball, but now think of it eight orders of

magnitude, smaller. and the basketball has to rub on the outside and in my nanoliposome, in the rubber, i put the drug ceramide. and it really stays well in that rubber and it doesn't become a toxic drug. and inside my basketball, i've

got air. inside my nanoliposome, i have a void volume for other drugs , because ceramide plus other drugs, one and one does not equal two, one and one equals 11. and that's the outside of my basketball, i got the knobs, so

i get to control the basketball. on the outside of the nano, i can put on knobs that make it stealthy and/or target specific cells like dr. kelly was talking about. we created a nanoliposome, a nanobasketball. more importantly, the two major

things that i want to announce tonight is number one, we're going to be in the clinic in the summer here at uva with a nanoceramide program. we just learned from the fda that one of my companies, keystone nano, has got an approval to actually take this

to the clinic so our preclinical package was accepted. and more importantly, the nih, national cancer institute, has given out one grand so far for what's called a first in man, first a two phase two, small business grant and that's going to fund the phase one trial here

at uva over the summer. so, that's the exciting news. nano is coming to uva. with that said, i want to now segue. nanotechnology enables precision medicine. dr. kelly talked about precision medicine, and what it is is

basically three different patients, you have three different individuals, breast cancer, breast cancer, breast cancer unfortunately. when we look at these two patients, they have totally different gene products driving their cancers.

there are mutations in these gene products, but the one driving this cancer is different from this cancer. it's even more confusing. because these two patients have the same mutated protein, but they have the mutations at different sites.

so all of a sudden now, you've got this conundrum, how do you actually target these specific mutations? and nanotechnology allows us to do that. so i can talk about precision medicine, but again, we go back to the master.

so what are we really doing? so basically, we go from information to messenger to action. dna, there's a mutation in the dna that through the rna network makes a protein that's mutated and that drives the cancer. and at uva, we can actually

sequence your genome at the dna level, we can use techniques to look at the rna, and we can look at the proteins to find if you have a mutated protein that's driving your specific cancer. that's individual precision and i want to stick to the protein because that's really

important. so we have kits that can be really quick, can do this now in an afternoon, sequence your whole genome, but this is much faster. we can look at the proteins that are driving your cancer, and we can target the therapy based

upon that. so for instance, there are certain breast cancers that are driven by a gene product called her2/neu which is mutated. we can do a test and say you have the her2/neu mutation, you don't. you're going to go onto therapy

called herceptin because i want to give this drug which targets that mutation. you're not going to go on it because you don't have the gene product and it really is not a good drug for you. so, that's precision medicine. we're doing it right now at uva.

but unfortunately, here's a little nasty secret, the number of drugs that actually go after mutated proteins, i can count them on my hand and maybe my toes. there's like 15. if we wait for big pharma to come up with true drugs that go

after mutated proteins, we're waiting too long. there's got to be a better way. and that better way is molecular based therapies. so, we have ways to design little pieces of rna. we call them small interfering rna.

and basically, we can target out specifically with a great deal of selectivity, the rna that's mutated. so we got unbelievable control. and this is what we call molecular based therapies. here's the problem, this srna is toxic, immunogenic,

inflammatory, and just like ceramide, if i gave it to you, it's lethal. how do you actually take this material and truly deliver it? and the good news is we've kind of done it. so this is a nanojacket. it's a calcium phosphosilicate

nanoparticle. think of it, calcium phosphates, your bone and teeth material. it's also a very, very, very, very small tums. and inside our little small tums is this green here. we can fill that full of fluoroprobes, drugs and the case

we'll talk about today, the srna. so i actually have some of these nanoparticles here. these are uv lights. so i'm going to keep it away from everybody's eyes, but these are the actual materials we see down there.

they've kind of dehydrated a bit because they're seven years old. do we have any physics majors out there by any chance? i've always said that and nobody ever raises their hands, but basic physics suggests that fluoroprobes, especially under light after an hour or two,

photo clenched, they photo bleed, they don't fluoresce anymore. here's the thing. these are seven years old. they've been sitting around my apartment and car for the last seven years. if they fluoresce, it's

physically impossible. the reason that nanotechnology works is we take materials and nano size them, you get new properties that are not explained by conventional physics, and you exploit those properties. so hopefully we'll turn down the

lights. hopefully you'll be able to see that. see them fluorescing? there's the green one. there's the blue one. we have a red one down here that dropped, but they still work. that's the beauty of

so what we have done, there's one nanotechnology. we got a million billion of them. that's one electron micrograph of one, and inside, we put the >> keystone nano assembles nanoparticles containing a therapeutic drug.

with trillions of particles per ounce, an iv solution packs a big punch. the nanoparticles circulate in the bloodstream. their structure and size, which is much smaller than a blood cell, allows them to travel in the body longer than free drugs.

to support growth, tumors create blood vessels to supply nutrients. but typically the vessels created by tumors are poorly constructed and provide small gaps to access the tumor. particles slip into cells and selectively kill tumor cells and

shrink tumors. more information is available at keystonenano.com. >> all right. so let's -- just last couple of slides and i can show you some data. here are the actual nanojackets. why do we call them nanojackets?

because they're dressed to kill. why did we select that? nature magazine did a great little piece on our technology and they put, "nanojackets dressed to kill," so as a company, we trademark that immediately. these are the individual

nanojackets, and more importantly, these are the ones that encapsulate the srna. this is the part where you look at. look at them. they look like m&ms. kim kelly was talking about her m&ms.

we created m&m. inside the middle is the calcium phosphate matrix. this little part where there's no kind of coloration, that's the srna. on the outside, we put a candy-coated covering, that's calcium phosphosilicate that

protects the srna. and more importantly, kind of works. so, i'm going to show you one piece of data. we took a breast cancer cell that is driven by two mutations. one is her2 product and one is something called pi3-kinase.

we love acronyms in science. we make them up. but basically, this cancer is driven by these 2 gene products. here we just gave the experiment, just saline, all these dark lines, those are the gene products. here, we actually gave a

systemic iv dosing of the srna nanojackets specific to her-2/neu and pi3-kinase. no staining. no protein. goes away. and in these experiments, 60% of the experimenters actually had regression of tumors.

so here's the vision because i'm going to leave you on. here's the true vision of what we're really talking about. think of an allergist, allergy shots, pollens out there, hay fever, ragweed, et cetera, you go in, you get tested, and you get specific allergy medication

given to you routinely that targets your specific allergens and then two years later, you come back in and you're retested and say, "yeah. we really took care of the hay fever, but now you got tree pollen allergies, so we now changed the allergens a little."

that's what we're talking about here. you come in, you get the precision medicine, we deep sequence the tumor, we do the biopsy, and we say, "your tumor is driven by a mutation in pi3-kinase and her-2/neu." we create the nanojacket with

the srna specific for your mutation. patient gets treated. then six months later, sometime later, you come back in because unfortunately cancers develop secondary mutations. do it again and say, "yeah, we really took care of the

pi3-kinase or her-2/neu, but now you got a new mutation. take it off the shelf, another srna." so we're going to be one step ahead of the tumor. we're never using the c-word here for cure. we're using c-word for chronic.

we want to take cancer and make it a chronic disease and this is the way we believe we're going to do it. and hopefully as the ceramide nanoliposome goes to the clinic in the summer, we're hoping this technology will end up here at uva in about another two years

as we go through the preclinical package, but truly, i like to end by nanotechnology holds the promise to enable precision medicine, so with that, i'm going to go offstage. we're all coming back and then we're here for questions and answers.

>> that was terrific. that was terrific. dr. kester, thank you so much. now you're going to have a chance to ask them questions. we're bringing out some chairs. and we've got two volunteers, i believe. the lights are so bright.

i can't see out there, but there are supposed to be two volunteers with microphones, i suppose, on each side, and you have to come out into the aisle to ask your question. it's -- we can't pass the microphones down so i know you have questions.

it's rare that you have a chance to ask experts like this about a subject as complicated as cancer, and best of all, there's no charge. this is absolutely free so take advantage of the opportunity. why don't you start lining up? where are -- where are our two

volunteers? there you are. there's one. oh, there's the other. why don't you start lining up next to each of the mic volunteers so that we're ready to go? and i see someone right here.

we're going to start with you, sir. >> i'll pretend it's one question, but it has three phases. these nano-vehicles delivery systems, are they always the same structure? >> no, they expand all of

material science, so we're now seeing phase one, phase two trials in the united states, everything from nanogold, nanosilver, nanoplatinum, nanoplastics, nanopolymers, nanodendrimers, nanoliposomes, and each one has specific properties that we can exploit

for different -- and i'd like to say we seek, treat an image with nano, and that's what we're doing right now in these trials. >> just if i could, the sirnas -- >> uh-hmm. >> in principle, you can do that for all cancers?

>> yes. >> let's go to this gentleman >> hello. last week i saw the segment on "60 minutes" about the poliovirus as a clinical trial treatment for brain cancer, and i wondered if you had any comments about that or if how

that -- how that's involved if your colleagues at another university are working on something, how it might affect uva? >> sure. as everyone in the panel would say, we share some of the most exciting research going on at

uva, but there's an exciting research in cancer going all around, over the country, and that trial at duke is a good example. we know for a -- we've known for a long time way back in the 1900s, physicians injected patients with bacterial toxins

as a poison, and showed some transient responses in terms of cancers going into remission. so, we know that the immune system is very important, and the immune system often is targeting viruses, so that actual therapy is not only delivering viruses, but

stimulating the immune system to kill off the virus, and since the virus is right next to the cancer, also kill the cancer cells. it's very promising. it's an early phase trial so we look forward to seeing if that will be successful.

>> anyone else? >> yeah. and here in my laboratory, we're modifying a cold virus called an adeno-associated virus. so, we can put those keys or peptides on the virus and get it to go only to the tumor and and then we can go in and get it

to make something that will--a protein that's toxic that will kill the tumor. so we are doing things like that here at uva also, but it's an exciting time. >> wonderful. another question here. >> i have a question about the

sirna since that was one thing that we got some detail on. when you did the test with the srnra and you came back with the blank thing, once you -- do you -- do you have to continue giving the sirna or does it come, you know, does it come back once you take that away?

>> that's an excellent question. and we're looking at the window of opportunity now with the srrna. we're looking at the dosing schedules. it will come back, and therefore, we believe that the nanojackets, which is basically

just calcium phosphate particles, would be well tolerated so just like you would take a chemotherapeutic regimen once a week for four, six, eight weeks, this may be a little longer chronic treatment, but we believe that we can actually be one step ahead of that cancer,

but at least the studies that we're doing right now, it seems like we have to continue treating with the srna's. with that said, the ceramide program, there are experiments we've done. in fact, we've done experiments here with tom loughran, some of

the leukemias where we actually give the ceramide nanoliposome, and it does very well, and then we take the ceramide nanoliposome away, and the tumors do not come back. in some leukemias, we're seeing true regression and true cures. so some of the technology, we're

hoping that we'll have that ability, but with the srna specifically, we may have to continue dosing. >> is the srna replacing the nra? i mean, the rna? nra, i'm -- >> so the srna is designed to

actually bind to the rna and degrade it. >> so it actually -- and it's very specific. this is great. only the rna that we believe is mutated, so basically it allows -- the whole idea here is that when you have one of these gene

products, they're really all over your body. any growing cell has pi3-kinase. only the cancer cell has to mutate to pi3-kinase, but the pik3ca is driving the growth of your hair, your gut cells, your white blood cells, all the side effects, so you don't want to

just kill all the pi3-kinase. that's the side effects. only kill the mutated pi3-kinase. that's what the srna allows you to do. >> and i just want to say that if you want details, we are so happy to host you guys in our

lab and give you as many details as you want. any opportunity i have to geek out, i'm really excited to do so -- and in fact, my husband will say, "what did you and all the other nerdtrons do today?" is how we start our dinner conversation, so.

>> that's marvelous term. geek out. >> and we're delighted you've chosen this field to geek out in. thank you, sir. let's go over here to this side. >> i have a question also about the sirnas.

>> so in in vitro models, when sirnas are used, there are a lot of problems with off-target effects, right? >> correct. >> so how have you been able to identify, i guess, beyond acting, which is pretty far from pi3-kinase that --

off-target effects don't exist? >> i think she's--this could be a plant. that's a really great question. so basically, there's a lot of data we're not showing you, but -- so we always give injections systematically, iv, and the nano has to not only

find the tumor, but has to find that mutated srna, and we have studies where we actually have cell lines where some are driven by the specific mutation, some are not. you add the srna to the cell line that, you know, doesn't have mutation.

nothing happens. you add it to the cell line that has the mutation, cell line dies. so, we have all these studies that show specificity, selectivity. and in addition, just as dr. kelly was saying, we have the

ability to do this lock and key. we can actually put targeting motives, little pieces of antibodies, little pieces of small molecules, little pieces of aptamers, we call them, and what they do is they selectively bind to certain proteins that are only expressed in the cancer

cell so we kind of cheat. we can get these nanos to go preferentially to the cancer cell and they get stuck there anyway because nanos love to go circulate and they go into the tumor, which has a very leaky environment because they -- tumors are starving.

they want energy. they want oxygen so they form a leaky vasculature. the nanotechnology gets stuck in the leaky vasculature. it doesn't get out and that's why it truly can target the tumor so that's why it's selective and specific we think.

>> thanks. >> excellent. excellent question. do we have one final question? terrific. it's a very fundamental question, but if you have a tumor cell in your body and your tumor cell is going to kill your

body, and therefore kill the environment of which the tumor cell lives, how do you explain that so that it's killing the very host in which it's giving it life, so we're working to kill the tumor cell but does the -- what's the science behind the tumor cell sort of?

does it think about, "well, i'm eventually going to kill my host and i'm eventually going to be killed?" does it care about that in sort of an inanimate way? >> so you're giving cancer a little too much credit. it doesn't think.

but it really does think because what it does, the new research is it's basically shutting down the body's immune system so the body cannot mount a defense against the cancer, and the new therapies are coming out, are resurrecting the immune system and say, "go after that cancer."

and that's going to be the new drugs that i believe will be a major advance in terms of the arsenal of drugs that we have for cancer. the--that's the difference between of a host pathogen kind of thing where you have a virus, kind of the cold virus, or

things like ebola or other things where you're playing these games of, "okay. how long do i need to multiply inside the body before i kill the host in order to survive?" cancer doesn't do that. it's a living thing, but it's a misprogram.

it's a mistake in the body. it's not its own single object or organism that's doing that kind of things. with that being said, some of the cool things that are out there in big data and some of the engineering computer modeling fields is to model it

like those kind of cat and mouse, "what do you need to do? how big does it grow? what's going on in order to bring it back?" and so taking some of those principles that i've already known from those kind of organisms, and bringing it back to see if that

can really change how it's -- how the cancer is treated. >> any other comments from the panel? >> one final question? all right. go right ahead. >> thank you all for sharing your information tonight.

it's so exciting for all of us to hear about it. i have a special interest in pancreatic cancer, so thank you for picking that and sticking with it. we need that. but i wanted to talk about we know that pediatric cancers

have great numbers as far as people participating in clinical what can we do to help people overcome their fear, their perceived thought of i'm not getting the best i can if i participate in a clinical trial and helping them understand that that's not the case at all and

that that really holds the answer for so many? >> so i wish i could give you a simple answer to the question. it's a combination of a societal awareness of the importance. it's clinicians and caregivers and advocacy groups, it's not just one thing.

we do understand that there are ways to focus next generation therapies and get people excited about outcomes, but it's hard work. it's hard work for us in general, so if there was a simple answer, of course, very smart people have thought about

this for a long time, they would have figured it out. we have to grind it every day. yes. >> and i'd like to add a comment to that. the perception that you mentioned that patients on clinical trials make it inferior

treatment to what might be the standard out there, first point is that all the standard therapies out there is really because of the privilege of the patients that went through these the second point is it's been very well studied that patients on clinical trials, regardless

of which arm they're on, whether they're on the better -- whatever turns out to be better, even if they're in the inferior arm, their outcome is better than patients in the community treated exactly the same. there's lots of reasons for that, but probably it's because

it's so much more careful and close monitoring of the patients as they go along. so i think we -- as rob said, it's been a problem for many years, but what we need to do is educate everyone, that this is really the way cancer therapy has been developed and it's not

an inferior outcome no matter what treatment you receive. >> last, last question. >> okay. absolutely. i'll make this short. again, thank you. this has been extremely interesting this evening.

this is a just kind of a follow-up to the clinical is there any -- and my only experience with clinical trials is -- was in 2008, so maybe it's changed a lot since then, but what is uva doing to make it more economically feasible for the patients to go through these

clinical trials? in 2008, my husband was in a clinical trial with sloan kettering end stage. we had a fight with the insurance companies to do it. it ended up costing us eight -- $8,000 out-of-pocket for four outpatient chemotherapies.

nobody told us it was $19,000 a bag, but what is uva doing to make it more -- i mean i think that's one of the big deterrence to clinical trials. >> you know, what i would say is is that it's not about just what uva is doing. i mean, over the last 15 years,

there's been an evolution in terms of the federal government's world view. if you are a medicare recipient, standard of care cost that go along with clinical trials are now mandated by law to be covered. you know, we live in an

interesting medical environment in the united states, and it's not a sole system payer system. many times, participation in clinical trials is actually more cost effective, but because we're dealing in a complex world, we have to basically, you know, again, as the

investigators, you can be assured that we spend a lot of time thinking on this issue because clinical trials are expensive to do. there's not a uniform answer other than decreasing the barriers to enroll patients on trials is what we do every day,

and some of that is economic. so, there's not one simple answer, but it is something that a lot of people think about, and we're making efforts to try to do what we can. >> as emcee, i have two final duties, one is to wrap on time and we're exactly on time.

the second and much more pleasant and important duty is to ask you to join me in an enthusiastic ovation for the four fantastic professionals who are trying to make our lives better. thank you all so very much. [applause]

>> no problem. >> this program was made possible in part through a grant provided by the national sponsors of "cancer: emperor of all maladies" coordinated through weta public television. [captioning performed by the national captioning institute,

which is responsible for its caption content and accuracy. visit ncicap.org] [captioning made possible by wvpt]