All Medicine Should Be Personalized


Leonard Zwelling

In his unique and insightful way, Siddhartha Mukherjee has once again distilled the cancer problem down to what we know and what we don’t.

He describes the previous “mutant-hunting” that was the earliest days of genomic medicine as being like the Saul Steinberg New Yorker cover that depicts a New Yorker’s world view as ending at the Hudson River. It seemed for a while that the alpha and omega of cancer research could be encapsulated using a gene sequencer and access to a chemist who could synthesize a molecule to target abnormal gene products. Dr. Mukherjee points out that both the “basket” trials of cancers with the same mutations and the “umbrella” trials where a type of cancer was sorted by its gene signatures for individualized therapy, left much to be desired in truly altering the outcome for patients with malignancy. Both Herceptin and Gleevec were false alarms. They were not the rule. They were the exception.

Cancer is more complicated. As Sidd says, you cannot ignore “the cellular environment…the milieu around the cancer…or the human body that is wrapped around it.” Correct!

Rather we ought to use all the tools at our disposal, including the stethoscope and the part that goes between the earpieces, to do the best we can for every patient, even if that doesn’t involve gene sequencing.

Basically, Dr. Mukherjee is arguing that we should not take too narrow a view of what constitutes precision medicine. Even the recent announcement about breast cancer uses genetics to determine when NOT to treat a patient with early stage cancer.

It is magical that we can look deep into the heart of a tumor’s DNA and discern some logic to what distinguishes it from normal cells. But more times than not, the number of differences separating normal from malignant is overwhelming and sorting through which differences really matter and which can be therapeutically exploited is no easy task. Perhaps the new immunotherapies may make the tumor’s DNA irrelevant, but then it appears that the immunogenicity or the immune susceptibility is also linked to the mutational burden of a given cancer.

Reading Sidd’s article once again reminded me that the only logical response to cancer—in the lab or in the clinic—is humility. It’s usually smarter than we are. As he quotes in his article, the earliest forays into the application of genomic medicine for clinical benefit were like the old joke about the man who lost his wallet looking for it under the lamppost because that’s where he could see.

If we ever truly conquer cancer, it is most likely that we will prevent more of it than we treat. My guess is that some day we might understand carcinogenesis thoroughly enough to stop doing what’s bad for us and do more of what’s good for us and even that may be different for each and every person because there is never just one us.

We are all born with a pre-existing condition—life. Cancer is just one of the ways the promise of existence, that it ends, is fulfilled. Nonetheless, we cannot stop trying to make our lives better and reduce suffering from this dreaded disease. It just might not be as simple as was hoped fifteen or so years ago. And there really is life beyond Tenth Avenue.

Medicine has always been personalized. It is practiced one patient at a time—always. Genomics is just one way to help the next patient. It may neither be precise nor precisely what the patient needs.

Leonard Zwelling