Stanford Medicine Newsletter Updates For the Local Community

 

A conversation with cancer’s biographer

New perspectives on a complex puzzle

Renowned cancer specialist Siddhartha Mukherjee, MD, PhD, author of the Pulitzer Prize–winning book Emperor of All Maladies: The Biography of Cancer

   

Siddhartha Mukherjee, MD, PhD, a graduate of Stanford University, is a cancer physician and researcher, and author of the acclaimed book The Emperor of All Maladies, often referred to as a “biography” of cancer. He is an assistant professor of medicine at Columbia University and treats patients at the Columbia University Medical Center. He will be the featured speaker at Stanford Medicine’s Health Matters program on May 10.

We often refer to the “war on cancer,” implying that this is a fight that is winnable. Is that a fallacy?


I think the word war complicates the matter. It implies there is a pitched battle, and for some patients it feels like that. But cancer is a puzzle, and you solve puzzles, which is in some ways a better metaphor. You don’t solve wars. I think it’s a very complex, very human puzzle. It’s not just a scientific puzzle. This is a profound struggle, a profound puzzle, and I think that metaphor is more appropriate.

You have described cancer as a “corruption” of the genes. Can you explain?


The word I often use is “distortion.” Cancer is unlike many diseases in that the very genes that allow cells to grow, if you distort those genes, you unleash cancer. Even cancers caused by viruses and environmentally caused cancers ultimately change the genes that control cell division. So that is the final common pathway.

Some of these genes seem to control processes that are more mysterious than we originally thought. Some of them control metabolism. They control how cells handle metabolic compounds. They handle how DNA is regulated. There is an air of mystery that remains unsolved about the link between these genes and cancer. Some of the burning questions now in cancer involve these genes.

We often refer to cancer as a universal disease, but is that really the case?

Cancer is not one disease but many diseases. Even with breast cancer, for instance, there is such a fundamental difference between breast cancer that is hormone-receptor positive and hormone-receptor negative. They really behave as fundamentally different diseases.

Why?

We still don’t really know and clarifying that is going to be one of the most important puzzles of our time. That discovery — the distinction

between hormone-receptor positive and hormone-receptor negative breast cancer—was made in the 1980s, and yet even today we are struggling to figure out why they behave so differently. It’s a reminder of the depth of information required to understand something as common as breast cancer, which we have been working on for centuries.

What have been the most significant leaps forward in terms of our understanding of cancer?

When I think about cancer, I try to think about it in terms of four different phases. We’re at the fourth phase now. The first big leap was the understanding that cancer is a disease of cellular origin and that it originates in one cell. It represents an abnormality in cell division and therefore can be treated or cured by cutting the cell out. Or that same collection of cells can be killed by radiation.

The second big leap came much later, in the 1970s, when scientists realized it’s a disease not just of cells but of genes. And it’s a combination of genes and environment. That second leap has given rise to things like targeted therapy. The third leap is that cancer is not only a disease of cells and genes but of the genome. That has given rise to a host of new therapies for cancer, including things that target pathways that are abnormal in cancer.

The fourth phase is what I like to describe as cancer as an organismal disease — that it emerges in the context of an organism. If you think of the cancer in isolation, you neglect the fact that these cells interact with other cells. For the first time we’re seeing therapies that focus on how to activate the immune system, how to prevent cancers from arising in the organism. It’s a more holistic view in a very particular sense, which is to consider the whole, which is a very important part of medicine.

What important things have you learned from your patients?


It’s not as if I’ve finished the learning process. I think the lesson you learn from patients is to listen and to listen with humility — to have a conversation. People think about medicine as a one-way conversation. There’s also an idea that there are two one-way conversations, one with doctor to patient and one with patient to doctor. But there is no reality to that. I’ve written that hope is negotiated and that our understanding of cancer and its outcomes is negotiated. Decisions about what to do are negotiated. There is a space between the total autonomy of the patient and the total paternalism of the physician, which is the space where real medicine happens.

What are the most promising new directions in cancer therapy?


There are hundreds of promising directions. I’m excited about the ideas of targeting cancer, either the genes or pathways or at the organism level using the immune system. I think it’s incredibly important to talk about prevention — from primary prevention (preventing cancers from arising in the first place) to tertiary prevention (preventing relapse or second cancers). The bottom line is there are many exciting things in terms of new directions.

 

 

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