Genomics and personalized medicine: Is it really different this time?

Genomics and personalized medicine: Is it really different this time?Another year and another annual meeting for the American Society of Clinical Oncology in Chicago. This is a meeting that regularly attracts many thousands of doctors, researchers, pharmaceutical folks and others interested in the science and business of cancer from around the globe to learn, to discuss, to persuade, to educate on the progress being made in clinical cancer research and treatment.

And like every year, there are themes that emerge, that tend to dominate the discussions. And there are other themes that aren’t so visible, that don’t get as much attention yet in my mind are equally important as they reflect not only on the item of the moment but on how we deliver on the promises we have made in the past and the hopes we all have for the future.

Clearly, the dominant and visible theme at this year’s gathering is personalized medicine.

What strikes me about this topic is that over the past year it has gone from a “niche” discussion to a dominant theme not only here at ASCO but everywhere I turn. I am even seeing routine television news shows and commentators talking about the promise of personalized medicine. A talk that I planned six months ago to deliver in a couple of weeks from now in Boston where I was going to discuss (once again) the promise of personalized medicine in cancer care is now passé. Everyone knows about it, thanks to the incredible coverage it has been receiving literally everywhere. Now anyone who has been paying attention to the evening news could give that talk. The topic is ubiquitous.

So what is personalized medicine? At heart, what this is all about is harnessing our exploding knowledge of the human genome and applying it to the treatment of severe disease for individuals based on genetic analysis. Our focus today is on cancer, but other diseases such as degenerative brain diseases also will be impacted by our knowledge of the human genome.

As I sat in a lecture yesterday afternoon on the topics of genomics and personalized medicine, I was amazed about how much knowledge we have garnered in what appears to be such a short period of time. We now are hearing about new approaches to analyze how cancer cells work to discover master regulatory cells. The promise, of course, now that we have insight into the pathways of how cancer cells work internally is that we can target our efforts to those master regulators and conquer them, thus converting the cancer cell back to normality. Sounds simple, but it’s not. And it has taken a lot of research to get us to that point.

So one comes away from those discussions imbued with a new enthusiasm that the cure is around the corner. We are almost there. We will succeed–hopefully in the very near term.

But then I pinch myself and say, “Really?”

I do not want to be misunderstood about what I am going to write next. I am very enthusiastic about the progress we are making, perhaps more so than any time in my career. This time may be different. At least a lot of people–including me–think so. But I have been here before, and I am seeing signs that give me a moment’s pause to reflect whether everyone could be so right.

I had a chance to see one of my colleagues from my early training days while walking in the hall yesterday. I took the opportunity to reminisce about some of our experiences back then. When we started our training we had the opportunity to work with a new drug for small cell lung cancer. We treated a patient with that drug–one of the first to receive it–and he had a miraculous response. Imagine how we all felt at that moment: we had witnessed a major advance in cancer treatment for a disease that was uniformly fatal in short order. We had a “win.” But it wasn’t the win we thought it was. As we gained experience and reality over the next many years, it became clear it was in fact a small step in a disease that has proven refractory to further advances decades later.

Why do I bring this up? Because as I recounted the memory with my friend I shared my concern that we may be seeing some of the same history repeat itself: drugs that work miraculously for diseases that are difficult to treat, generating huge enthusiasm, but as we get more experience we find that our successes don’t last a long time except for a small number of patients.

And my colleague said, “This time is different.” Everyone is saying this time is different. I certainly hope so. But maybe I am not completely convinced.

There is something in investing called a contrarian indicator: when the cab driver tells you his latest stock tip or a major national newspaper has a front page headline extolling the success of the stock market, it’s time to get out. Now that personalized medicine is hot on everyone’s lips, does that mean the same for its promise?

What we tend to forget are the lectures that others have given here at ASCO meetings in the recent past talking about the frustrations of their careers working with a single mutation, such as KRAS. We forget the promises of other targeted therapies that haven’t held up as expected. We forget the enthusiasm we had when Gleevec® put chronic leukemia under control (a truly remarkable event) and the disappointment when other targeted therapies came along and didn’t have the same degree of benefit for other cancers.

Last evening I attended a lecture about the promise of immunotherapy in cancer treatment. Truly amazing advances in harnessing the immune system are now resulting in treatments that finally have given some hope to patients with previously refractory cancers. This is meaningful progress.

But during that lecture, the speaker flashed a picture of a legendary scientist/clinician who was one of the major leaders in immunotherapy research. The picture was from the cover of Time–in the mid 1970′s. I remember that cover and I remember the story that appeared in the magazine. It was the incredible story of how we were going to harness the immune system to help our bodies recognize the cancer “invaders” and get rid of those cells the same we got rid of viruses.

The speaker last night went on to extol the promise of immunotherapy. What he did not dwell on was the fact that the same promises were made 40 years ago. Along the way, the failures have been legendary. Things didn’t exactly turn out the way we expected when that article was written a long, long time ago. Yes, we now have some successes but we have no cures. We still have a way to go. It has taken a long time for immunology research to deliver the goods. No one back in 1970 thought it would take that long. This was exciting research back then. They said, “This time it’s different.” Promise you: I was there, and I do remember. And it wasn’t different–perhaps until now, 4 decades later.

I hope this time is different. I hope my caution is misplaced. I hope the suggestion that this is going to be more complicated than it appears at this moment is flat out wrong. And nothing I write here today should suggest that do not stand in awe of the incredible researchers–both those who work in the laboratories and those at the bedside–who are among the most dedicated and brilliant people that I know.

We have been witness to irrational exuberance in the past. And I hope we can deliver on great promises, and will deliver on those promises. It just may not be as easy or convenient as some would like to have us believe. We still have a long way to go.

J. Leonard Lichtenfeld is deputy chief medical officer, American Cancer Society. He blogs at Dr. Len’s Cancer Blog.

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  • Remedios Moscote

    I used to do research in this field (cancer genomics) before defecting to medical school – your caution isn’t completely unwarranted. I still do very much believe it’s the future of genomics and personalised medicine in (at least) oncology
    medicine, but unfortunately a lot of the hype forgets the huge genotype
    –> phenotype bottleneck that we are currently facing. To explain to those not familiar with the field – we are sequencing genomes at a dizzying rate, the problem is not getting more genomic data (although storing it can be challenging! haha) – it’s making sense of that data from a physiological point of view, for example – is this SNP (single nuclear polymorphism) actually physiologically relevant to this disease state, or is it just another passenger mutation? To be able to design targeted therapies based on genomics we really need to delineate this link between genotype and phenotype and that is often a hugely difficult and complex task when you are dealing with diseases that are not monogenic (caused by a mutation in a single gene) in origin (i.e most of them).

    Having said that, I believe that this time it is a little different than say, the graveyard of broken promises that has been ‘sensations’ like gene therapy and immunotherapy – mostly because this isn’t just about a single type or types of therapy. Genomics itself isn’t a therapy – it’s just another picture of our physiology – it’s like we are upgrading to a camera with better resolution. This better resolution will enable a more precise insight into the aetiology of various diseases. Just like the advent of microscopy and histopathology enabled us to differentiate certain pathologies that, clinically, appeared to be similar…genomics will lend itself in a similar way to allow us to differentiate diseases that histopathologically, appear similar, but aren’t similar at all on a molecular level (mostly talking cancer here but you can extrapolate…).

  • BionAlexHoward

    We must not forget that progress in many fields occurs exponentially. So while for many years it feels like we’re treading water, we might actually almost be there. The rate of change in our ability to treat the disease is not linear. I’m an optimist about our prospects of controlling cancer in the near term, using systems biology and genomics. It will require a switch from population based medicine to personalized medicine, and IMO the biggest hurdle is regulatory.

    -Bion Howard, MS2, MUSC

  • Kevin L. Wallace

    Have you considered and applied the epigenomic principle of uncertainty in this field of interest and speculative health care service value?

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