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Treatment Can Make Cancer Stronger

But New Cancer Treatment 'Revolution' Under Way
By
WebMD Health News
Reviewed by Louise Chang, MD

June 10, 2008 -- What doesn't kill cancer cells makes them stronger, Duke researchers have observed.

Doctors use radiation and chemotherapy to destroy cancer cells. About half of patients are cured -- that is, all of their tumor cells die.

The other half of the time, some tumor cells survive treatment. These cancer cells are more aggressive than they were before treatment, says Mark W. Dewhirst, DVM, PhD, professor of radiation oncology at Duke University.

"When you give a tumor treatment, whatever cells survive are going to be more resistant to that treatment," Dewhirst tells WebMD. "Those not killed are healthier cancer cells."

This does not mean radiation and chemotherapy don't work. It does mean that additional new treatments will be needed. And to know what treatments will work best, Dewhirst says doctors need to know how cancer cells survive radiation and chemotherapy.

The key may be a protein called HIF -- hypoxia-inducing factor. Government, university, and drug-company researchers are racing to develop new drugs that inhibit HIF. But patients may not have to wait that long: Existing drugs, already approved by the FDA for cancer treatment, turn out to be potent anti-HIF agents.

Why is HIF suddenly a big deal? It's the key to a different way of looking at cancers.

A 'New' Theory of Cancer

It's been known for about 50 years that solid tumors have areas that don't get much blood -- and that cells in these areas survive without much oxygen.

For a long time, this was thought to be an interesting curiosity. But now the ability of cancer cells to survive without oxygen -- to become hypoxic -- is being seen as a driver of cancer progression.

"A cancer cell that doesn't get much oxygen is like a rat deserting a sinking ship," Dewhirst says. "It will do things to try to help itself."

So the cell does four things:

  • It sends out a signal for help, asking the body to grow more blood vessels in the tumor.
  • It changes the way it eats, switching from oxygen metabolism to anaerobic metabolism.
  • It prepares itself for the day it gets help, building defenses against a burst of oxygen molecules that is toxic to anaerobic cells.
  • And the cell is going to try to get out of there -- to invade a blood vessel and go somewhere else in the body to grow.

Each of these things makes cancer worse:

  • New blood vessels let the tumor grow larger.
  • Cells that don't use oxygen are much less sensitive to chemotherapy and radiation.
  • Cells resistant to bursts of oxygen (oxidative stress) also are resistant to some of the ways the body gets rid of cancer cells.
  • Cells that wander spread cancer to distant parts of the body.

Johns Hopkins researcher Gregg Semenza, MD, PhD, calls this discovery one of the four "major conceptual advances over the last century which have the potential to revolutionize cancer therapy."

Part of that revolution has been Semenza's discovery of HIF-1. HIF-1 is the signal that transforms a cell from an oxygen-using cell to an anaerobic cell.

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