Wednesday, 21 June 2017

Colon Cancer Stages And Prognosis

heffner: i'm alexanderheffner, your host onthe open mind. the emperor ofall maladies, cancer, is a subject weconfronted recently with national institute ofhealth foundation leader maria freire, specificallywith regard to the untapped potential ofthe human genome project as a first line of defenseagainst the disease. in announcing his decisionnot to run in 2016, vice president bidencalled for a moonshot

to cure cancer in hisremaining months in office. "i know there aredemocrats and republicans on the hill who shareour passion to silence this deadly disease,"biden reflected. today we evaluate theprognosis for eradicating cancer in the contemporaryindustrial age with one of the world'srenowned immunologists, laurie glimcher, dean ofweill cornell medicine. so of laurie i ask,what's the prospect of

genomic research forenhanced prevention, detection, and treatment...and what are the odds that we realize thatreal moonshot -- a cancer vaccine torid it from theplanet forever? glimcher: wellthank you alexander, it's a pleasure tobe on your show. when i think ofcancer prevention, i think ofcancer vaccines, but i think more broadlyof all that we can do

to prevent cancer. and part of that iscoming up with a vaccine that will work likethe vaccines we have for hepatitis b orflu or polio. now, the field of cancervaccinology is actually in a very early stageand so i think it's an, at an exciting pointand i think eventually we will figure outsome of the proteinson tumor cells that can be attackedjust as you would attack

a virus or a bacterium. we're not there yet. when i think of vaccines,what does vaccines mean? it means you're tryingto prevent a disease. well there are a lot ofways to prevent cancer or to treat cancer. i like to think though ofmaking cancer a chronic disease rather than focusjust on curing cancer. think abouthiv/aids for example,

um, as an analogy. so, hiv/aids fromconverted from a lethal disease into a chronicdisease because basic scientists' fundamentalresearch was done that illuminated aspects ofthat virus and allowed the generation oftherapies likeantiretroviral therapies. and so now hiv/aids isnot a lethal disease, it is a chronic disease. but most patientsstill have some virus

in their system, right? i think if we couldget to that with cancer, turn it into a chronicdisease that we could control withtherapies, uh, we would have come avery, very long way. so when vice presidentbiden talks about a moonshot, yes, um,we need to devote and dedicate moreresources to cancer, but i think we needto do it like we didit for hiv/aids,

which is to workfrom the bottom up, start with fundamentalresearch then translate that research intonew therapeuticsfor our patients. you know, it's, youcan compare that to um, leaving no stone unturned. the fundamentalscientists, the ones who make thebasic discoveries are, are turning overthose stones and the translational researcherswho translate those basic

discoveries into newmedicines for patients are looking where thestone has alreadybeen unturned. heffner: can therebe... honestly speaking, can there be an assault oncancer without an assault or a war on carcinogens? glimcher: let's talkabout cancer prevention, which is reallywhat you're sayingmore broadly. statistics would have itthat maybe two thirds of cancer is treatable...well let me put it adifferent way.

the decrease in incidentsof death from cancer is largely attributableto new medicines ortherapeutics. perhaps a third isattributable to changing our environment, andthat includes ofcourse smoking which i believe accountedfor probably 20 percent of deaths from, certainlyfrom lung cancer, more than thatfrom lung cancer, but from cancer overall. there are otherbehavioralthings that need

to be done, so obesity isa risk factor for cancer. lack of physicalactivity is a riskfactor for cancer. and finally, changingour propensity to screen ourselves for canceris also a preventive medicine, so breastcancer can be prevented by mammograms, cervicalcancer can be cured, essentially cured ifyou do regular screening tests, the papsmear tests, looking for humanpapilloma virus

and now there's avaccine against humanpapilloma virus. every kid shouldhave that vaccine. look at what happenedwith hepatitis c. hepatitis c was adevastating disease but because fundamentalresearch was done in hepatitis c, itis now curable. it is now absolutelycurable with newmedications. so this is transformative. and hepatitis c oftenled to liver cancer,

so just think what wecan do now by screening everybody to see ifthey have hepatitis c and then if they do,treating them nowwith the drugs that cure hepatitis c. i mean we've, we'vecreated entirely new classes of drugs thanks tovery generous support over many years fromthe government. and we could talk a littlebit later about how that support isdwindling and theimpact that's going

to have on us. heffner: let'stalk about it now. glimcher: okay,we'll talk about it now. so i've been inthis business for oh, 30 years or so,and i have neverseen as restricted a budget in thefederal governmentas i have today. and this is particularlyfrustrating because in the last 5 to 10years, a revolutionhas taken place in science and medicine.

we've mined thehuman genome, we can visualizeorgans and tissues with astonishingclarity, we were neverable to do that. we handle big data, we dosophisticated molecular imaging, all of theseadvances now allow us to really move forwardand get discoveries that our scientists makein their laboratories into new therapeuticsfor patients. and at the same time, nihfunding has become

very constrained. if you look atthe nih budget, it's about 30billion dollars. if one were to correctthat for inflation, it would be now about47 billion dollars. the budget has actuallydeclined in real dollars 25 percent overthe last decade. and that's justunsustainable because we are losingyoung scientists.

we are losing seniorscientists who can no longer afford to runtheir laboratories. heffner: so if you wereto give vice president biden direction in termsof the public policy conducive to makingthat budget work, what we have now workin a way that suggests we absolutely mustinvest more dollars, what is the transparentoutput that you and your colleagues mostwant to demonstrate

to the governmentand to taxpayers, look, here is whatwe can accomplish, look at whatwe've done already? glimcher: indeed look atwhat we have done already with cures for hepatitisc and making hiv/aids a chronic disease,but that requiresa lot of funding, so just thinkabout it this way. if we were to doublethe budget of the nih like presidentclinton did, we would,

we would raise it to60 billion dollars. now that would result ina 100 dollar contribution from each american. in other words,30 cents a day. think about going tostarbucks or dunkin' donuts and how much youspend on one cupof coffee a day. for over a year, if youdrink one cup of coffee five days a week ayear, you're gonnaspend 800 dollars. so this is not abig deal. right?

to double the budgetis very doable and we have bipartisansupport for it. we have... heffner: despitethe bipartisan support, the forces havenot allowed you and your colleaguesto make this effort. glimcher: i thinkthere's a lack of understanding whichis partly our fault as scientists and physiciansin not communicating well enough with the public.

but there's a lack ofunderstanding of how importantbiomedical research is. so thinkabout, let's take, let's take alzheimer'sdisease as an example. we are already spending200 billion dollars a year taking care ofalzheimer's patients, out of a budget, of atotal health care budget of about 2.9 trillion. in the year 2040,one out of everythree individuals

over the age of 85 isgonna have alzheimer's disease and that is goingto amount to a health care cost of about 1.2trillion dollars. what is the only wayto deal with that? we have got to find away to prevent alzheimer's disease, treatalzheimer's disease, or at minimum delayits onset for 5 years. look at the agingdemographics ofthe population. and it's a scary,scary situation.

heffner: i want totake us back to cancer for a moment, if onlyto evaluate that communicationquestion that you raise. considering theenvironmental risk factors, what is aplausible strategyto effect change? glimcher: the fourmost common cancers that account for about80 percent of all cancer deaths are lung, breast,colorectal cancer, and prostate cancer.

now think about preventivemeasures for those. well when we thinkabout lung cancer, the biggestenvironmental factor iswithout doubt smoking. um, that would makea huge impact andhas made a huge impact on theincidence of lung cancer. we have to keep pushingthat and making it clear to everybody whysmoking is so dangerous. i think a lot ofpeople still don'tunderstand that. left over from the tobaccocompanies insisting

that cancer, that lungcancer had nothing to do with tobacco. think aboutcolorectal cancer. if one has a routinecolonoscopy at the age of 50 and thencolonoscopies thereafter as the physicianrecommends, you could largely preventcolon cancer, youcould detect it in its very earlieststages and cure it. take cervical cancer.

if you have a papsmear every year, there's no reason todevelop cervical cancer. if you havethe hpv vaccine. so you're right, thereare clearly environmental factors that candecrease the incidence and death from cancer. i would still say thoughthat the majority of cancers cannot beprevented at this point, but they can be treatedand they can be treated

two major ways. i, i like to think of theprogress that's been made in cancer, the, thestunning progress that's been made overthe last 5 yearsfalls into 2 buckets. and one bucket is whatmaria freire talked about which isprecision medicine, the idea that eachperson's tumor is unique and has a unique geneticfingerprint or signature. and if you can developa drug that attacks

that mutant gene,you can get incas—some cases an astonishingresponse, a reallyastonishing response. i'll give you an example. we had a patient at weillcornell who came in with bladder cancer thathad been spread to many different organs andthis individual was, was pretty much ondeath, at death's door. it was discovered thatthat person had a genetic mutation for which we didhave a drug but which is

usually, or neverseen in bladder cancer, it's usually seenin breast cancer. but cancer can no longerbe classified according to the organ inwhich it arises. it has to be characterizedin terms of the genetic mutation that exists. and this individualwas put on this drug, it's calledherceptin, and had an astonishingresponse to it.

so that'sprecision medicine. heffner: and that's ahyper-localized approach in effectrelative to a vaccine, you're looking at acertain set of a, of a populationcohort that is small. glimcher: well it's adiff—diff—very different approach in the sense thattumors put on the surface these proteins that arespecific only to the tumor and aren't presenton normal cells.

and the idea of a cancervaccine is to immunize an individual againstthose tumor proteins. precision medicine isdiving into the dna with a knowledge thateverybody's tumor has a unique geneticprofile and you want to be able to identify thatspecific piece of dna that has becomemutated and that isdriving cancer growth. heffner: you mentionedrisk factors before but when youwere looking atthe four most,

uh, frequentcancer patients, you mentionedsmoking, what aboutthe role of um, what we're eating? obesity? obesity, uh, makesyou um, predisposedto which cancers? glimcher: with obesity,there is an increased risk for many cancers, andhere's where diet and nutritioncertainly do come in. there's some veryinteresting work

on the microbiome,which is the wholeother universe of dna that liveswithin us in our guts, on our skin, in mucosalsurfaces and there's very clear evidence thatthe structure of that microbiota, but particularkinds of bacteria that are there caninfluence somebody's weight and this is a reallyexciting study thatwas done by uh, a researcher at washingtonuniversity named jeff gordon who showed that ifyou take the microbiota

from an obese individualand put it into a mouse, that mouse willgain weight on ahigh fat diet. but if you put themicrobiota from a lean mouse, from a leanhuman, into a mouse, that mouse will beresistant to high-fat diet or so-calledwesternized diet, a mcdonald's diet. and that tells us thatmanipulating this whole other genome,the microbiome,

could be very, veryuseful indecreasing obesity, decreasing diabetes, whatwe call metabolic syndrome and these are allrisk factors for cancer. they're also risk factorsfor alzheimer's disease. heffner: when youthink about those risks, you, you said despiteall of those risks, we are likely to encounteras a population various forms of cancer,um, that are out of, really that areout of our control.

glimcher: well in 2012,we had diagnosed about 14 million new cases ofcancer and there were about 8 millioncancer deaths. by 2030, the predictionis there will be about 22 million new cases ofcancer and an increasing number of deaths,about 13 million, and that's in part becauseof the aging demographics of the population. the biggest risk factorfor cancer is aging.

and as we all grow older,and the population as a whole growsolder, we're goingto see more cancer. precision medicine isone way to attack cancer and it's proven to bevery effective but, remember thatlike hiv/aids, you're going to needcombination therapies. that's the, the lessonthat has emerged, so you can get remarkableresponses to a particular drug if you have aparticular mutation

but tumors like thehiv virus are very, very clever andthey mutate and become resistant to it. so the key to hiv/aidswas to say let's give a patient multipledifferent therapies at the same timeand that makes the virus much lesslikely to mutate. that's the next frontierin precision medicine. let's figure out howmany mutations a patient

has and whether wecan attack themsimultaneously. so precision medicineclearly is an exciting, very exciting advanceand has you know, much promisein the future. the other bucket that wehaven't talked about yet, which is near anddear to my heart as an immunologist iscancer immunotherapy, which has beenamazing in the lastjust few years. and this is a fieldthat's actually very old.

it started with a newyork city physician named william coley,who was a surgeon and he noticed that inpatients that he had operated on to removetheir tumors, thosepatients who developed an infection afterwardstended to do better, their tumors tendedto stay in remission. and so he thought wellthere must be something in the infection, theremust be some presence in those bacteria,some, some thing thatthey're making that

is activating the immunesystem to kill the tumor. because your immune systemshould kill your tumors, probably all of us haverandom rogue cancer cells floating around in ourbodies but by and large, in the majority ofcases, our immune system circulates and acts as asurveillance mechanism and kills off thosefew tumor cells. so dr. coley generated aproduct he called coley's toxins which headministered to patients,

they were bacteriallysates and some patients had a response to them. that, that soonbecame um, uh, passã© because of theemergence of radiation therapy and chemotherapy. but it has rearedits head for 30 years, immunologists have triedto say how do we activate the immune systemto kill off tumors? that's the, one ofthe functions of theimmune system.

and that has bornefruit in an amazing way just in the lastfew years and... heffner: in the timewe have remaining, how do you scalethat nationally? glimcher: as you pointout, cancer vaccinesare in the future. and they could bevery effective. checkpointblockade, which isacting your immune system to recognizethose cancer cells and kill them is anothervery promising approach

and there have been somecheckpoint blockade drugs out in the marketnow that willrelease the brake on t lymphocytes,the t lymphocyte is your major killerof tumor cells. and the, the advancethat was maderecently and the, the realization that cameabout was that rather than directly activatingthose t lymphocytes, it was better to take somepressure off the brakes by attacking receptors thatinhibited t lymphocytes,

and hence thegeneration of drugs, uh, like yervoy and opdivoand ketruda and others in the pipelinethat activate your t cells by releasingthe brakes. and those haveproven very, very powerful indiseases like melanoma, lung cancer, and manyothers that are still in clinical trials. so that's, that's anotherreally exciting approach

and then finallyum, there is arecent approach of actually transferringin activated t cells that have beengenetically manipulated to specificallyattack the tumor. so you might say wellthose are rather costly and cumbersome approachesand while that's true, i think they have made anastonishing difference to cancer patients. so i imagine that thatis an area that's

going to expand further,we're gonna get better and better at activatingthose t cells and making them more specificfor the tumor, and i look forward to,to seeing that happen. heffner: and knowingthe market forces here that really determineultimately whether or not these treatments gointo mass production, what is the obstacleto, in your mind, outside of thenecessity to be funded,

what is the obstacle,um, what is the barrier in your way frommaking these, uh, immunotherapiesavailable to thewidest population? glimcher: checkpointblockers are available to the majority ofthe population. they are expensivebut you know, when you think about it,it costs a pharmaceutical company about 2.5 billiondollars to develop a drug and only perhaps 20percent of drugs actually

are revenue-generatingfor a company. so, when you think ofthe costs of cancer care, one can imagine that drugslike checkpoint blockers or transfer of these tlymphocytes are actually cost-saving, just astreatments for hepatitis c, while expensive,overall save money by preventing hepatitisand hep—hepatocarcinomain patients. but this is a conversationi think we all need to have about uh, costof drugs and making them

affordable to not just allamericans but all citizens of the world, and thatis an important goal that we should strive for. heffner: let's sayyou had all the money in the world, right? what would be yourprescription... by 2020 or whatever date youwant to set tobanishing cancer? glimcher: i'd ratheruse the term make cancer a chronicdisease thanbanish—banish cancer.

the national cancerinstitute asked for a budget of 5.8billion this year. president obama suggesteda budget of 5.1 billion. if you think of theamount of funding that was put intohiv/aids, that worked. it worked. it worked becauseit brought brilliant scientists into the field,who discovered basic things about the hivvirus that allowed them

and the translationalresearchers and the clinicians tocome up with new drugs, and the pharmaceuticalcompanies to come upwith new drugs. right now thenih budget is, in contrast to a countrylike china where they're pouring moneyinto basic research, the nih budget is leadingto an exit of the most talented scientists andresearchers from academic medical centers andbiomedical researchinstitutes.

we just can'tallow that to happen. because once you closedown your laboratory, you can't just rev it upagain if you're able to finally get a grant. so academic medicalcenters have turned to other sources for funding. they've turned to theprivate sector for funding and they've turnedto philanthropistsfor funding. and i thinkthat's great.

i think that the marriageof academic medical centers and academicianswith the private sector is a very, is a marriagemade in heaven because it's the best way toget basic discoveries from the laboratoryinto new therapeutics for our patients, so... heffner: we'll haveto leave it there, but thank you so muchlaurie for educating us today on thefuture of cancer.

glimcher: my pleasure. heffner: and thanks toyou in the audience. i hope you join usagain next time for a thoughtfulexcursion into theworld of ideas. until then, keepan open mind. please visit theopen mind website at thirteen.org/openmindto view this program online or to access over1,500 other interviews. and do check us out ontwitter and facebook

@openmindtv for updateson future programming.

No comments:

Post a Comment