The Life and Times of Bcl-2, Part I

By Josh Baxt
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Cancer can be likened to a comic book super villain. Malignant cells divide recklessly and develop a form of immortality, making their rampant cell division even more threatening. Unlike many normal cells, which are programmed to live for a defined period, cancer cells resist these mechanisms and survive when they shouldn’t.

These days, we have a much better understanding of why cancer cells refuse to die—even when subjected to toxic doses of chemotherapy or radiation. But 20 years ago, the idea that cells could develop resistance to a natural process called apoptosis (programmed cell death) was barely part of the scientific conversation. In 1986, John Reed, M.D., Ph.D., Sanford-Burnham CEO, Professor and Donald Bren Chief Executive Chair, together with other researchers who discovered the first anti-death gene Bcl-2, began to unravel the mechanisms behind apoptosis and their relevance to cancer.

“It was a great ah-ha moment in cancer biology,” says Dr. Reed. “No one had paid much attention to the cell death side of the equation where tumor growth is concerned. When it comes to accounting for the number of cells in the body, it’s a simple case of credits and debits. Cell division makes more cells, adding to the credit side, and that was already known about cancer. The new revelation was that cell numbers are normally kept in check by programmed cell death—the body’s way of offsetting credits with debits to achieve a zero balance. In cancer, it’s like there’s a freeze on spending. The cancer cells refuse to die and pile up in organs until the patient is overwhelmed.”

Apoptosis is particularly important in cancer because misbehaving cells are supposed to self-destruct to maintain order. When genes go awry, or when normally stationary cells become detached to roam freely through the body, those misbehaving cells are expected to give up their lives for the greater good. Bcl-2 and other anti-apoptotic proteins short-circuit this process, allowing these rogue cells to thrive and spread.

“For cancer cells, Bcl-2 is like having diplomatic immunity,” says Dr. Reed. “They can do whatever they want without the normal consequences that maintain an orderly society.” But even more insidious, the same mechanisms that keep these cells from dying also help them survive against our best cancer treatments.

“Another important revelation was that chemo and radiotherapy induce apoptosis,” says Dr. Reed. “However, anti-apoptotic proteins protect cancer cells from these therapies. We realized that Bcl-2 could block the therapeutic effects of virtually every anticancer drug that existed, as well as radiation, and most of what the immune system can throw at the tumor.”

The Life and Times of Bcl-2, Part 2

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Josh Baxt

Josh was a Sanford-Burnham Communications staff member.

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