NYT series on genetically-targeted cancer treatments

When you have been diagnosed with cancer, as I have, you quickly grow accustomed to "friendly cancer spam." Friends, relatives, and well-meaning acquaintances routinely forward you a gazillion identical links to whatever this week's hot cancer news headline may be.

So it was for me with this New York Times story on Lukas Wartman, a leukemia doctor and researcher at Washington University who developed leukemia. As he faced death last Fall, his cancer genome was sequenced by his colleagues.

What was revealed then led to a treatment plan that targeted the specifics of his genetic makeup. And so far, according to Gina Kolata's report, that experimental treatment plan has been an amazing success. Snip:

Dr. Ley’s team tried a type of analysis that they had never done before. They fully sequenced the genes of both his cancer cells and healthy cells for comparison, and at the same time analyzed his RNA, a close chemical cousin to DNA, for clues to what his genes were doing.

The researchers on the project put other work aside for weeks, running one of the university’s 26 sequencing machines and supercomputer around the clock. And they found a culprit — a normal gene that was in overdrive, churning out huge amounts of a protein that appeared to be spurring the cancer’s growth.

Even better, there was a promising new drug that might shut down the malfunctioning gene — a drug that had been tested and approved only for advanced kidney cancer. Dr. Wartman became the first person ever to take it for leukemia.

And now, against all odds, his cancer is in remission and has been since last fall. While no one can say that Dr. Wartman is cured, after facing certain death last fall, he is alive and doing well.

Suffice it to say that this stuff is relevant to my interests. It is routine for breast cancer patients like me to receive genetic screening for the BRCA mutation, and sometimes a few additional known genetic factors. But there is so much that we do not know, and a growing sense that this infinite array of genetic unknowns could lead to more saved lives, and better quality of life for those of us who have been diagnosed with the disease.

I know I'm not alone in feeling like the treatment I am receiving now will one day be perceived as blunt and barbaric, when genetically-targeted therapies like the ones outlined in these stories become the norm. Those of us undergoing the brutal routine of chemo, radiation, and surgery to keep cancer at bay long for the day when more precise technologies can stop the disease without so much collateral damage.

And then, there is the greater hope that maybe one day all of this will lead to the other "c-word."

A cure.

Read the full article: "In Treatment for Leukemia, Glimpses of the Future."

Part two in the series: "A New Treatment’s Tantalizing Promise Brings Heartbreaking Ups and Downs"

And part three: "A Game Changer in Revealing a Cancer’s Prognosis."

There is a related item in the Economist. Here is the referenced study in the journal Nature from researchers at Washington University.

(image: Shutterstock)


  1. This is notable…  From the article:  “And the scientists who did the data analysis did not charge.”

  2. I think I just get sadder and sadder any time someone sends me a cancer-related link, because none of them has anything to do with my cancer, because it’s one of those rare ones that isn’t being widely studied. So it’s just another “yep, thanks for thinking of me but this won’t help either.” :-

    1. I hear ya. I hope that one day, one of the links *does* relate to your disease, and that an awesome new genetically-targeted therapy comes down the road that helps you.

      Hang in there, and I am sorry you are going through this, too.

      1.  Thanks Xeni. I’ve been following the stuff you’re going through (quietly) and wish you the best of care and outcomes.

        1. Quiet comfort. My mom has been told twice in her life (once at age 24 of skin cancer, then 37 of Hogkins) she has cancer and will not survive. She is a very tenacious and stubborn women. Both those doctors have since died and she survived her treatments, now is 64. As she puts it, “No Friggin doctor is going to tell me I’m going to die till I’m good and ready.” 

          Was it her will power or the actual medical procedures? Little of both perhaps. 

          My best friend died of Hogkins, I still miss him 16 years later. He gave up.

          Never give up.

          1.  *smile* Thanks. I’m pretty stubborn and have for too much stuff to do yet before I go. Maybe in a few years, they’ll be saying this genetically-targeted treatment is something to try for me too.

    2. My wife’s was one of those too. Fortunately, it just progressed to a stage that’s more widely studied. :(

      Anywho… keep that hope alive. There are mechanisms that appear across types of cancer. The more we learn about all cancer and all applicable fields of study, the better for everyone touched by this horrible disease.

      And, as one of my wife’s doctor’s told her almost 4 years ago, they’ve learned more about her type of cancer in the past 2 years than in the previous 18 years of his career combined. I’m sure this goes for most cancers out there.

      1.  I wish your wife the best of care and outcomes. I like to think we of the rare cancers are directly affecting the studies that are being done since we’re providing cases for them to actually study. And that can only be helpful. :-)

    3. Your friends and family may be misinformed about your diagnosis, but there is actually quite a bit of research in rare cancers, because of the orphan drug act. If you search for your cancer on clinicaltrials.gov, there’s a good chance you will find active clinical trials specific to your disease. Good luck to you.

      1.  That is a really useful link, thank you for sharing it. One of the things I’ve learned is that patients have to take an active role in their treatment and do a lot of the research and legwork. Even though our doctors are highly educated and informed in their field, they can’t be on top of everything 100% of the time.


  3. I agree, it does seem “blunt and barbaric”; my wife was as damaged as if she had been in a medieval sword fight when she came out of surgery. It took years for the full effects of that to wear off. But, it did seem to work, and 15 years later she’s still here; so we take what we can get. Good luck with your own battle.

    1. We had superannuated surgeons who were doing radical mastectomies with node dissections on every woman with a lump.  And this was well into the era of good staging and less invasive surgeries.  They would tell their patients how important it was to be sure and then nuke them from orbit.

  4. Crazy idea BWJones’ comment gave me: cancer patients get together DIY Bio style and fund via Kickstarter a lab in which they can get their genomes sequenced to the depth that was done for Dr. Wartman. 

    1. G, there’s an idea for that approach, it was designed for Breast Cancer, and it’s called Pink Army. Andrew Hessel built it:

      I am not sure how is that going these days, but a model similar to that is the future, I think. Maybe even Pink Army itself.

    2. That would be awesome. Sadly, the real issue would be targeting the malfunctioning gene, which DIY currently has no hope of doing. And even if you DIY sequence your genome plus your cancers’ genome, no lab would ever accept that info, and would insist on doing (and charging for) their own sequencing.

      You would have to DIY the same techniques the researchers did to engineer a drug to shut off the malfunctioning gene but not a correctly functioning one, say a few Hail Marys, and inject it into yourself.

      The alternative, of course, is to wait for Big Medicine to do it, and they’re not going to do it without the assurance that they can extract all your money, because we all know we’d pay every damn cent we had, and all the ones we don’t have, for a cure for cancer. And then they’d only start doing it on the ones with the terminal stage of cancer.

      It makes me cry. Fuck.

      1. It sounds like in his case they used an existing drug so they didn’t have to engineer that. The data seemed to be what made that decision possible. There are likely many cases in which such decisions to use an existing treatment might be made if they just had the genetic analysis to base it on. However, would doctors accept the genetic analysis…your point is well taken on that. 

      2. no lab would ever accept that info, and would insist on doing (and charging for) their own sequencing.

        Maybe the Kickstarter needs to fund a lab too then?  Or maybe some will do it for the positive exposure and/or charity?

      3. This is not as unfeasible as it sounds. Insurance companies pay out millions of dollars for standard treatments for cancer patients, which generally involve a sequential shotgun approach of first-line, second-line, third-line, fourth-line, and salvage therapies, in order from highest success rates to lowest. Sequencing the whole genome and targeting the specific genetic defect (if possible) would cost tens of thousands of dollars retail, but would still be vastly cheaper than the whole nine yards described above. The real question is how many people would be lucky enough to have an addressable genetic defect with an already-approved drug on the market. We don’t have many of those “slam dunk” types of drugs just yet. The development of a diversity of targeted drugs will be more of a challenge than making the sequencing affordable. You can now sequence the human exome for on the order of $1000, and the analysis can be largely automated using bioinformatics software.

        1. On the other hand, cheap sequencing of both host and cancer could enable that genetic taxonomy of cancer thing I heard about on some TED talk or other (was it this one?). Which might help in focusing research rather than using, as you say, the shotgun approach.

  5. I think the impulse of “no fair” is understandable and perhaps justified by the current debate on cost of medicine to society. However, it is entirely possible that the current debate on how to reduce the cost of medical care has it all wrong. My opinion here is not a popular one, but from what I see of what goes on in health care, I think everybody is always getting short-changed. Even the people who pay and use alot of expensive health care.  When one compares the cost and engineering of the F22 or even a car or DVD player or freak’n ipad.. these things all make medicine seem like a poor stepchild. Why doesn’t Krugman switch “alien invasion” for “war on death”? I’m sure there are some practical reasons why I’m wrong, but it is a useful thought experiment.

    1. The issue in your comment comes down to our priorities as a country and our priorities are defense.  We as a country (USA) spend more on defense than the rest of the world combined…  Think about that for a minute, then repeat it out loud.  More on defense than the rest of the world *COMBINED*.  If we as a country really wanted to invest in a cure for cancer or blindness or diabetes, we’d invest those dollars where it mattered, in basic and applied research, which, by the way, tends returns more to the economy than just about any other segment (NIH data).

  6. This personalized medicine is the future, and it gets cheaper every day.  However, it is not easy, nor is it as simple as learning a new technique.

    A tumor is a mess of broken alphabet soup.  In fact, sequencing the same tumor multiple times from different samples will reveal a different genetic sequence each time.  Predicting which mutation is causing the unchecked growth is like finding a needle in a haystack, and there are almost always multiple such mutations present in a moderately advanced tumor.  It can even vary from cell to cell in the same tumor!  People seem to think that finding the correct mutation is like finding the misspelled word in a manuscript, but it is more like finding the correct waldo in a beach scene filled with perfect waldo impersonators.

    It is not “Big Medicine” that is holding back this technique.  For one, it is because it is in the infant stages of medical research, because it is unproven.  If you read Part 2 in the series above, you’ll see that it didn’t save the second patients life, nor arguably extend their lifespan significantly.  Big Medicine is providing the targeted bullets as fast as it can, it is up to the doctor and the sequencing labs to determine which target to shoot for.  This gets cheaper every day, but keep in mind it is still RESEARCH and not yet ready for the bigtime.  Unfortunately, medical research is such that while people deserve the latest and greatest, we scientists need to make sure that we’re not peddling snakeoil.

    The current paradigm of FDA regulation, pharma research, and cancer treatment are all askew relative to personalized medicine, because they are still in the mode of finding a “breast cancer drug” or an “ovary cancer drug” versus finding a drug to target the correct mutation.  This is not due to greed or mismanagement as much as it is because cancer is completely unlike any disease we have tried to cure.

    TLDR: we scientists are trying as hard as we can.  “Big Medicine” is helping to do their part, they aren’t evil and trying to steal your money.  Before this technique is ready for primetime, we need to use the scientific method and figure out how to do things right, which is much harder then people think.

    It’s great to see current scientific research in mainstream publications, but heartbreaking to see it getting peoples hopes up before it’s ready.

    1. This is helpful — I didn’t know that: “People seem to think that finding the correct mutation is like finding the misspelled word in a manuscript, but it is more like finding the correct waldo in a beach scene filled with perfect waldo impersonators.” 

    2. I was going to post this exact same response…thanks to gsilas for doing it. 
      We are honestly working as hard and as fast as we can. And some of us are working on both fronts of the battle (I’m an oncologist and a basic scientist). And this (NYT) story is awesome for Dr. Wartman. But the practical reality is that, if they were to make this a realistic series, they’d publish another 48 stories where a specific, targetable mutation was found and the patient received the targeted therapy and it did F*** all and 6 months later the patient was dead. Because that is the unfortunate reality.

      I work at an institution where nearly every rare (6 months) response to treatment.

      I don’t mean to downplay the importance of the work done by the group at WashU, or the importance of any individual life. I only mean to temper the “OMFG…why can’t we all have all our tumors sequenced right now…are you trying to kill me?!?!” with a little reality.

      1. I don’t know much about cancer but I do know the sequencing part is going to be comparatively very cheap within a few years, and maybe that will do some good. There must be other angles though like many new targeted drug delivery methods and things that we have frankly not thought of yet. 

        1. The price of sequencing was supposed to have plunged by 1998, which was why they started the the Human Genome Project.

          1. It has plunged dramatically to the point where the analysis is the costly part.  As I write this I am doing a preliminary analysis of a human sample that just came off of our Illumina hiSeq2000 sequencer.  Raw sequencing cost — about $3000.  Analysis cost — much higher unless the analysis is “common”.  And if the analysis does show something interesting — say a cancer causing agent — the cost to target that will be very high.  Dr. Wartman was lucky to find out that his cancer was treatable by an already known cure.  

            I am not sure I agree with bigfatlamer that “they’d publish another 48 stories where a specific, targetable mutation was found and the patient received the targeted therapy and it did F*** all and 6 months later the patient was dead” because if the targetable mutation is found and we have the therapy then the cure rate should be non-negligible.  But certainly I would agree another 48 (or 480) stories should be published where the mutation was not found or the mutation is not targetable.

          2. Re: Rick Westerman

            I would tend to agree with bigfatlamer.  An under appreciated aspect of tumor genetics that has been recently discovered that I mentioned in another comment is the genetic heterogeneity.  The mutation rate in tumors is so high that there is never just a single mutation that we can easily screen for and target; at best, we can detect all the mutations and attempt to whittle that list down to the potentially harmful ones which regulate mitosis, for example.  Detecting the mutations following sequencing is trivial, selecting for the harmful ones is much less so, and doing so correctly is extremely difficult.

            In an ideal scenario with early tumor detection, there may be a single harmful mutation that we can target.  But, more likely is an array of harmful mutations, and even knocking out the most damaging leaves an intact field of blood vessels that are ready to supply the next most harmful mutation with nutrients.  That is why part of the reason remission is so common, and how tumors gain resistance to chemotherapeutics like bacterial colonies do to antibiotics.

            Early detection is, and will always be, on of the most important factors.

          3. re: gsilas

             Detecting the mutations following sequencing is not “trivial”. It is an active area of research. There is currently very little agreement between the five or so mutation callers that are in development. It’s a very, very hard problem.

          4. In Re: to Rick Westerman (it wouldn’t let me reply to him…we’re too deep now)…. Would that it were so but the stark, clinical reality is that, even in tumors where a targetable mutation is found, a drug is available, and there is clinical activity, the rate at which tumors can bypass that single, targetable mutation with another mutation or 10 approaches 100%. 

            We actually have amazing targeted therapies (think vemurafenib for V600E mutated melanoma or crizotinib for EML-ALK4 fused lung cancer) but they’re unfortunately not curing (m)any people. Block pathway X (driver mutation) and pathway Y (passenger mutation?) emerges and your magic drug (which goes for $10K/month BTW) is less effective than an aspirin.

          5. “……It has plunged dramatically to the point where the analysis is the costly part.  As I write this I am doing a preliminary analysis of a human sample that just came off of our Illumina hiSeq2000 sequencer.  Raw sequencing cost — about $3000…..”
            Regrettably, the people running these operations are basically temps who don’t know/don’t care what goes or what comes out, and lab managers who will OK nearly anything to keep their numbers up.   You may make the best typewriter in the world, but it won’t help that team of monkeys crank out King Lear. 

    3. it is more like finding the correct waldo in a beach scene filled with perfect waldo impersonators.

      I’m not following you there.  If you can find the correct Waldo, they aren’t perfect impersonators.

      “Big Medicine” is helping to do their part, they aren’t evil and trying to steal your money.

      Some are, some aren’t.  It’s not really that black and white, is it?

      1. Right now, we can’t find the correct Waldo.  Re: bigfatlamer, above.

        A more complicated but much more accurate analogy, imagine a beach scene of perfect Waldo impersonators (each representing a genetic mutation), at least one of which has a gun in his pocket and severe mental illness (the active, problematic mutation).  Many others have knives and guns (also harmful mutations).  Even if we use an advanced metal detector, we will have difficulty separating the innocuous Waldo’s from the harmful ones.  We’re currently working on making our advanced metal detector smarter and our profiling more accurate using computational analysis and whole genome sequencing, but there could be 10 psychotic gun wielding Waldo’s and you will be damn lucky if you can identify all of them.

        And regarding Big Medicine, there are always some bad apples among any group of people, but we scientists who are busting our asses trying to help take offense to the widespread, blind cynicism that we frequently face (note: I work for a cancer center and not pharma).

    4. Don’t dump the FDA just yet, because we still have to  weed out bad science from folks  like the people at  Duke who were faking the data so they could spin off their company, when they weren’t busy with their interoffice/extramarital affairs. 

      1. I wasn’t intending to dump on the FDA, just point out one blockage for the adoption of personalized medicine.

        Currently clinical trials focus on populations of a certain cancer, but not a certain mutation.  To target mutations with clinical trials would require vast and widespread sequencing of every potential enrollee, with +95% discarded for lacking the desired mutation.  Thus, the clinical trial model is a blockage for personalized medicine.

        The alternative proposition that was popularized by Andrew Grove (where safety, not efficacy is measured) would allow experimental cancer drugs through, which could then be administered as last resort to patients with the targeted mutation.  This makes a lot of sense for cancer, but could be disastrous for nearly every other disease.—What those “scientists” (ugh) at Duke did was so reprehensible, it is mind boggling.

        1. There are actually a small number of trials currently open that do this right. The one I’m most familiar with is called “MOTHER” and enrolls patients with lung and thymic cancers into one of 6 or 7 different pathways based on mutations discovered (or not) in their tumor samples. Each pathway then has 3 or 4 drugs at any one time. It’s kind of a randomized Phase I trial. The downside is that there’s no comparison to standard of care therapy so, while we’ll probably learn what works, we won’t know if it’s any better than what’s already out there.

        2. It’s becoming more common for clinical trials to include at least a subgroup with a specific target mutation. The real problem is matching drugs with specific mutations that can be tested. It is my understanding that the FDA is vigorously encouraging companion diagnostics and looks favorably on genetic analysis in cancer trials, when possible.

  7. Here are two relevant links to large scale tumor sequencing studies (that aren’t primary literature behind a paywall).

    2011 – Heterogeneity of genetic mutations among breast cancer –

    2012 – Heterogeneity of genetic mutations within a single tumor –

    While it is easy to take a pessimistic look after reading the second article, I am greatly inspired by just how quickly our understanding of cancer is progressing, even now.  There is so much more to learn, and every little bit improves treatment across the board.

    1. The rate of change in science based largely on the accelerating rate of data accumulation and our ability to analyze it gives hope for a lot of things including a cure for cancer. What if like the influenza M1 protein (and no, I don’t confuse influenza with cancer) there might be some universal commonality to cancer that we have not found yet. Right now it looks like a forest but there might be that one tree in every forest that if you kill it, the rest dies. Wild speculation but I’d still guess someone out there is thinking along these lines.

  8. I know I’m not alone in feeling like the treatment I am receiving now will one day be perceived as blunt and barbaric, when genetically-targeted therapies like the ones outlined in these stories become the norm.

    Little-known fact: in addition to the transporter, Leonard McCoy avoided time travel whenever possible.

  9. Did you see this website:  https://www.23andme.com/  I haven’t been able to focus properly but this certainly fits with the discussion.  Hope you are healing.  Think of you all the time.

  10. I recently read the Walter Isaacson biography of Steve Jobs, and as I recall Jobs also had this type of genetic sequencing done for his cancer.  (I think, at the time, for a cost of roughly $100,000)  Further, because Jobs had a private jet at his disposal, he was able to get on organ donor waiting lists in two states, and as a result indeed did get his liver transplant in Memphis, Tennesse rather than in California where he lived.  I don’t begrudge Jobs for this, because I’m sure if I had his wealth I would have done the same to try and live a little longer, but to me those two stories just highlighted even more that in the United States health care for the wealthy is very different than health care for the 99%

    – TWR

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