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A Cancer Talk With Pulitzer Prize Winner Siddhartha Mukherjee

Tony Hagen @oncobiz
Published: Wednesday, Dec 16, 2015

Siddhartha Mukherjee, MD

Siddhartha Mukherjee, MD

Pulitzer Prize-winning author of The Emperor of All Maladies: A Biography of Cancer, Siddhartha Mukherjee, MD, was the celebrity guest at the 25th anniversary celebration of the first bone marrow transplant (BMT) performed at the John Theurer Cancer Center (JTCC). The 1990 operation, led by Andrew L. Pecora, MD, served as the foundation for a quarter-century of rapid growth and achievement in cancer treatment and research, JTCC officials said during their gala event at the Hackensack, New Jersey campus.

The event featured a panel discussion with Mukherjee on cutting-edge developments in cancer, as well as reflections on that first BMT operation. “It requires special courage to be part of the leading edge in the treatment of cancer–especially on the part of patients,” Pecora said. He discussed his pioneering work, his anxiety as a young doctor with such a huge responsibility, and his success.

Pecora, vice president of Cancer Services and chief innovation officer at JTCC, said the BMT patient, Leonard Vena, reassured him by saying that it was a no-lose situation for the doctor. “If I die, I get to rejoin my deceased wife; and if I live, I get to see my beautiful daughters grow up,” Pecora recalled. Since then, JTCC has performed 6000 BMTs and enjoys prestigious certification for the procedure.

In an interview with OncLive, Mukherjee, who practices oncology and hematology at Columbia University and whose book was named one of the 10 most influential written in English since 1923 by Time, discussed new developments in cancer treatment and the potential for conquering this scourge once and for all.

OncLive: It’s been 5 years since you wrote Emperor. What has surprised you about the directions cancer treatment and discovery have taken since then?

Dr Mukherjee: The signal that’s so overwhelmingly positive has been immunological therapies. By the time Emperor was done, immunological therapies were just on the horizon. The first clinical trials had barely been completed and we didn’t know how long the responses were going to be, whether they were going to be durable, and whether the idea of activating your own immune system against a cancer would even have any legs.

We now know that idea has enormous potential over and over again within diverse groups of patients, and it’s now becoming a spectrum of therapies, just not one, ranging from so-called checkpoint inhibitors that change the way the immune cells can be activated, in the context of cancer, all the way to genetically modified T cells that hunt out your tumor and kill it. So now, there’s a whole menu of options in immunological therapy, and I think that’s probably one of the most exciting areas right now.

What may not have turned out as expected?

One of the hopes in the 1990s and the 2000s—particularly when oncogenes and tumor suppressor genes were originally isolated—was that you could take all of these cancer-causing genes and find small molecules that would go and turn them off or turn them on like locks to keys. Some of them have turned out to be that, and, in fact, the first fleet of molecules that came about was phenomenally successful—Gleevec being a wonderful example of that.

Facts are facts; one of the things that have been surprising about the cancer world is that many of these genes are not so amenable to the development of small molecule drugs. They aren’t druggable. Maybe we’ll find new chemistries that will allow them to become druggable, but these are challenging the frontiers of our known chemistry right now.

Thankfully, at the same time, one of the features of the immune system is that, give or take, it doesn’t particularly care what mutations you have in the cancer cell. Now, combining targeted therapies with immunological therapies has obviously been of great interest and has been very successful when it’s been tried.

How has being an author and a writer affected your work in medicine?

One of the things it has allowed me to do personally is to focus on some questions that are deeper than I would otherwise have imagined. It’s taken the intellectual pressure off. It’s created a kind of moral relief, because you look at the history and you say, “Look, some of the people who really made differences in the field thought about things for a very long time.” Bone marrow transplantation is a great example. They waited for a very long time until the idea matured.

It takes money to achieve things in medicine, yet federal funding for cancer research has been described as insufficient. What can be done about this?

One thing that’s very clear is that the National Institutes of Health (NIH) has lost a substantial amount of funding in real dollars over the last 10 years. Some of that loss of funding has been picked up, thankfully, through cancer-focused organizations—the Leukemia & Lymphoma Society being one of them. Large advocacy campaigns have also taken up some of that gap. But, even so, the funding problem remains very acute.

I’m personally involved in a large effort called ACT for NIH, a widely publicized effort to restore NIH to appropriate levels of funding. What is on the docket is to try to raise $12 billion over the next 3 years, not only for the NIH but also for the FDA, because you can’t have the NIH operating without an FDA. You need an equal partner so that the ecosystem of new therapies can be brought to life across the board. This is not just for cancer but also across the board for Alzheimer’s disease and Huntington’s disease—all these other diseases that remain challenges. This is a vast bipartisan effort and it goes by two names: one is 21st Century Cures and the other is called ACT for NIH. I’m involved, and there have been multiple trips to Congress to try to create a platform to restore the funding.

Meanwhile, Vice President Joe Biden has talked about a “moonshot” to cure cancer. Are we situated to accomplish something like this?

Well, before you get the moonshot you have to create the infrastructure to be able to go to the moon. Now, for cancer, we know what that infrastructure is. It involves basic research, translational research, clinical research, all the faculty that allow all of this to happen—the delivery of care, and the continuity of care, and the entire ecosystem of hospitals, and physicians, and physician-scientists who make all of this happen. It’s a big ecosystem with lots of participants. Everyone needs to be motivated to be able to do that work. Therefore, the moonshot, of course, is sort of the top of that pyramid, but at the bottom of the pyramid, you need that entire ecosystem of human beings.

How will our moonshot chances be affected by the value transformation in physician pay?

Ultimately, medicines and medical care have to be appropriately compensated, otherwise people will not be able to deliver the kinds of care that they deliver. One of the promises in cancer medicine is if the medicine is truly transformative, then people will come and access it in whatever manner possible. Some of it will be fee-for-service, some of it will be paid through a variety of mechanisms, but the main piece is to find the transformative therapies. We’re at that phase right now.

The appropriate cost will be settled once we have transformative therapies. You take a historical example: Gleevec changed the biology, changed the epidemiology, changed the way we think about chronic myelogenous leukemia so deeply that it would have been meaningless to ask questions about how we pay for Gleevec before Gleevec existed. Once it came about, we clearly found the mechanism to appropriately reward the inventors of the drug, get it to patients at a price point that patients can find at least within the bounds of reason. It obviously lies outside the economic reach of many people but within the bounds of reason, for instance, for Medicare.

It really depends on inventing those transformative medicines, figuring out what their real impact is, and then bringing them to people at the right level at the right time. We will do that as we move along. I think the community oncologists, scientists, the FDA, researchers, medical care units, hospitals like this are figuring out that landscape as we speak.

Besides pay, oncologists talk about long hours, administrative workload, recruitment difficulties, and burnout. Is this profession losing its luster?

I think doctors are fundamentally attracted to the human qualities of the profession, and the human qualities of the profession will remain forever. Doctors want to heal people. That will remain the core of what attracts them. New developments in cancer will continue to attract people to the profession.

When the first chemotherapies were successful in certain kinds of cancers—leukemias, lymphomas, among them—it brought a whole host of young energy to the field, because now people wanted to use these tools and to deliver them to patients in a compassionate, thoughtful, intelligent way. I think this cycle keeps going.

For people in medicine, there are really two kinds of things that sustain you in the long run. One of them is the humanistic quality of medicine, the fact that you believe in giving compassionate, thoughtful care to patients on a day-to-day basis; and then there is the excitement of bringing new ideas into the world, and I think a combination of those things will sustain oncology for a long, long time. It’s the most exciting profession. I think it’s the most exciting thing to do right now in medicine.

Would you like to predict where you think we’ll be with cancer treatment 20 years from now?

Some cancers, I think, will be very, very recalcitrant, but I have little doubt that we will cure several incurable cancers in the next 20 years. I think the problems about healthcare delivery nationally and internationally are not going to go away very quickly. There will be major challenges.

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