Biology in the News Explained

Review of Mukherjee, “Emperor of All Maladies”: We need a different paradigm for cancer treatment

Why is cancer approached so differently from chronic but incurable, deadly diseases such as HIV, diabetes, and heart disease? This question is not explicitly asked by Dr. Siddhartha Mukherjee in his 2011 history, “The Emperor of All Maladies: A Biography of Cancer” but is essential for making sense of the narrative that he presents.

Essentially, the short answer seems to be that the expectations and assumptions for how to deal with cancer took the wrong fork in the road (i.e. cure vs. management) decades ago, and we are still paying the price by refusing to see that we are in a cul-de-sac which continues to cause widespread, unnecessary misery.

The notion of “cure” has been a stumbling block in cancer treatment ever since the word was co-opted to raise money for the cause starting in the early 1950′s. How we view the disease now was probably affected a lot by the story of fairly common childhood cancers, which is where the modern way began; perhaps the notion that a child should be saddled with worrying about controlling cancer for his or her entire life just seems too bleak. (And yet, there are dangerous chronic conditions appearing in childhood which require constant vigilance throughout life, such as type I diabetes.)

Courtesy Wikimedia Commons

Courtesy Wikimedia Commons

Perhaps it was more the man who embodied the notion of finding a cure who set us onto the wrong path so early. Dr. Sydney Farber, with only the best intentions, began a single-minded crusade against childhood leukemia in the 40′s, making his first breakthroughs in 1948 — meaning, with toxic treatments, he added up to six months of survival for a few patients. Unfortunately, this notion of adding a few months to a select lucky few as a “breakthrough” has persisted to this day, in which new chemotherapeutics are routinely approved when they extend the lives of a minority of patients by a similar amount, or even less. Ironically, this standard has gotten us further and further away from focusing on the best approach to truly help people, let alone cure them.

Finally, it’s a bit easier to understand and even sympathize with doctors pushing the idea of “cure” so hard, when one looks at the data for childhood cancers, for indeed the progress on these since Farber’s days has been much superior to that of adulthood cancers. Interestingly, Mukherjee does not have any citations for possible reasons for this, or even offer any speculation, but his detailed narrative of how our knowledge of various types of cancer grew and how current targeted therapies work (and my own study of this problem) does offer one possibility: the resistance of cancer to treatment by drugs, as with all evolutionary processes, is mainly about genetic variability in the population of cancer cells, and it seems possible that adult cancers tend to harbor a bigger variety of mutations (i.e. pathways to resistance) than do cancer cells in a much younger body.  Although many children suffered greatly and died horrible deaths in Dr. Farber’s largely unregulated experiments, he had enough success that the idea of cure for all seemed tantalizingly close. But as far as adults are concerned, the starkness of the raw data make the rest of the story clear: since the official declaration of the “War on Cancer” in 1971, there has been almost no meaningful progress, despite constant announcements in the media that we are finally on the verge of a great breakthrough that will provide a cure.

But despite this solid success with some childhood cancers (whose cures still entail great suffering and highly increase the risk of secondary cancers later in life — for after all, most cancer treatments currently part of the “standard of care” are strong carcinogens in their own right) little seems actually changed in the last eighty years. Mukherjee quotes a 1937 Fortune Magazine article that asserted that cancer research was stuck in a rut due to inadequate funding, comparing the amount spent unfavorably to the amount people spend to watch football games. But while we still argue about the economic priorities of the U.S., the amount of money per se is probably not the main stumbling block anymore, as funding for cancer research has exploded nearly as much as the salaries of pro athletes, but with little to show for it in the clinical setting.

This is a point that Mukherjee doesn’t quite seem to grasp: the cancer research literature is rich with all sorts of different approaches showing different amounts of promise, very few of which have made it to clinical trials. An obvious conclusion when one becomes even somewhat familiar with this area (and one understands basic concepts in evolutionary biology, which is crucial to preventing to the commonly observed resistance to treatment which is really what ultimately kills most advanced cancer patients) is that multiple approaches at once — probably combining judicious use of chemotherapy (rather than the blunt-force carpet bombing we engage in now), generalized immunotherapy, and antibody-directed treatments, would be a good approach to explore, in the context of a management (rather than false “cure”) paradigm. Instead, the typical approach to advanced cancer treatment remains giving patients one drug at a time, and hoping it works; there is no testing to determine if a patient is a good candidate for a particular drug, despite plenty of information available to do this. If a patient is lucky enough to happen upon one drug that works for awhile, he or she is still nearly always doomed in the end because of developed resistance to that drug (which often involves cross-resistance to other chemo drugs because many of them work through similar pathways, and because cancer becomes more aggressive in the process of being selected for more defensive mutations).

So, we are stuck with a system which continues to give advanced patients false hope for cure, while treating them in a way which essentially guarantees a hastened death, even without considering the debilitating “side effects” of standard cancer treatment, which often enough kill in their own right. (Although there has been somewhat more measurable success with preventing recurrence of patients diagnosed at earlier stages, there has not been nearly as much as the propaganda would have you believe, because our increasing fanaticism with routine screening means that many of the diagnosed would never have developed advanced cancer in the absence of treatment anyway.)

“Emperor” is indispensable as a comprehensive history of how we got where we are today in the realm of cancer treatment. And yet, the huge disappointment with the book is that Mukherjee, instead of seeing the paradigm for cancer treatment as broken, seems to be so entrenched in the middle of it himself that he cannot imagine another way, and lamely suggests that we all be content just to wait patiently as the slow trickle of targeted therapies — which have admittedly made a big difference in a few isolated cases — perhaps continues. He never questions that framing cancer treatment as a “war” and focusing the goal on “cure” was the correct path to follow, even as he graphically recounts absolutely brutal fallout from this “war”, in the guise of treatments such as radical mastectomies and the STAMP (solid tumor autologous  marrow program), both eventually abandoned in disgrace as they were belatedly shown to be no more effective than other available therapies. These “therapies” were overused in the first place because of the obsession in the cancer community with pursuing “cure”, which persists to this day. One of Mukherjee’s problems as someone ostensibly analyzing the situation is that he, as most people who have not been trained in rigorous scientific and statistical methods (doctors are generally not), gets too easily swayed by the personal, anecdotal heartwarming stories of successfully treated patients who we label as “heroes”, embodying the myth of the brave underdog overcoming all odds to “win the battle” with cancer, even as the slew of cannon fodder all around these few succumbs, day in and day out, virtually ignored.

But there is a better way, alluded to above, which is starting get more research attention. Scientifically grounded work in immunotherapy and other (relatively) non-toxic treatments, and their combination with more traditional therapies used in a different way (e.g. low doses of some chemotherapeutic agents which turn out to act synergistically with immunotherapies) are starting to break through, not only in media reports of these areas of research but in a growing number of clinical trials, and even a few oncologists’ offices. But this is not enough, because we remain constrained in our thinking as a society by the obsession with “cure” and making “war” on cancer. We must get past these confining notions by thinking clearly about our goal: is it to provide notches in the belts of doctors who seem content to succeed with a tiny percentage of their patients in eliminating their cancer for good? Or should it be to provide the longest possible, high-quality life left to the great majority of us who will never draw the winning number in this lottery? Mukherjee succeeds in showing clearly how we got mired in this deep trench, dug over the decades by a complex mix of financial interests, politics, and dominating personalities, and it won’t be easy to get out. But while it seems like it would be an upheaval as a society to start thinking about cancer, for most people, as a chronic disease to be managed over the long term in an intelligent, science-based way, rather than to continue down the dead-end of mindless “hope” that means horrible suffering to patients and their families and friends on the way to often premature death, this is a goal worthy of the effort.


2 Responses to “Review of Mukherjee, “Emperor of All Maladies”: We need a different paradigm for cancer treatment”

  1. Amit Agarwal says:

    Few days back one of my friend urged me to read this one, written by young doctor!

    So started reading this book! What an amazing book this has turned out to be so far!! Great storytelling about CANCER!! Interesting , entertaining and informative…

    Shall complete it in few days.. yet I urge you to read this book whether you like cancer or not, whether you like non- fiction or not or whether you read novels or not!! as this unravels the mystery of the malignant disease called CANCER!

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