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Dr. Len's Cancer Blog

The American Cancer Society

Genomics And Personalized Medicine: Is It Really Different This Time?

by Dr. Len June 01, 2013

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 Magazine--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.

Comments

6/1/2013 9:19:12 PM #

Gregory Pawelski

I've been enamored by immunotherapy research, ever since I read the one 1991 study based on the concept of "in situ vaccination" based upon biologic response modifiers in an assay. In the 1960's, tumor immunology was probably the hottest field in cancer research. Then again, in the early 1980's, with the work of Rosenberg at the NCI with IL-2 and "LAK" and "TIL" cells. The immune system is obviously important. It is a natural approach to cancer therapy. It's good to see the resurgence of aggressive cancer vaccine research. Is it different this time?

In regards to personalized medicine, a number of clinicians, reported in the ASCO Post, have felt that the problem with the way cancer research is conducted is that the biology of the disease is so complicated that personalized medicine is still mostly only a promise. Targeted drugs for cancer haven't panned out to the extent hoped. Although a few might work sometimes or for a short time period, the effects have not been significant or durable. And many are more toxic than expected.

Companion diagnostics and their companion therapies are what's being pushed as "personalized medicine" as they enable the identification of likely responders to therapies that work in patients with a specific molecular profile. However, companion diagnostics tend to only answer a targeted drug-specific question and may not address important clinical decision needs.

These companion diagnostics are being used to predict responsiveness and determine candidacy for a particular therapy often included in drug labels as either required or recommended testing prior to therapy initiation. Laboratory oncologists suggest that diagnostic tests in the current "one-test/one-drug" embodiment will not adequately cover decision support needs as physicians become inundated with more biomarker data likely to be interrelated, nuanced and at time even contradictory.

Gregory Pawelski

6/2/2013 4:42:13 PM #

Daniel Corcos

Personalized medicine is a dead end, due to the inability to perform randomized trials. One has to find a global strategy against cancer, like this one:

onlinelibrary.wiley.com/.../abstract

Daniel Corcos

8/9/2013 8:16:20 PM #

MIchael Misialek

As a pathologist and strong patient advocate, your article really resonated for me. Please take a look at an article I wrote about the value of pathologists. Thank you.
commonhealth.wbur.org/.../meet-your-pathologist

MIchael Misialek

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About Dr. Len

Dr. Len

J. Leonard Lichtenfeld, MD, MACP - Dr. Lichtenfeld is Deputy Chief Medical Officer for the national office of the American Cancer Society.

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