Treatment Can Make Cancer Stronger
But New Cancer Treatment 'Revolution' Under Way
WebMD News Archive
A 'New' Theory of Cancer continued...
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
- 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
HIF: Key to Cancer Treatment Success?
"It's been shown that in a variety of different cancer types, those with
most HIF-1 have the worst outcome," Semenza tells WebMD. "The basis for
this is the fact that HIF-1 controls the expression of hundreds of genes that
play critical roles in cancer biology."
One of the first researchers to start looking for drugs that target HIF-1 is
oncologist Giovanni Melillo, MD, of the U.S. National Cancer Institute (NCI).
After screening hundreds of compounds for anti-HIF activity, Melillo and
colleagues made a surprising discovery: A number of existing cancer
chemotherapies turn out to inhibit HIF.
The most potent, Melillo says, is a drug called topotecan, marketed under
the brand name Hycamtin. It's already approved by the FDA as a second-line
treatment for ovarian and small-cell lung cancers. So why isn't this drug
already revolutionizing cancer treatment?
"The key to this treatment is the dose," Melillo tells WebMD.
"For chemotherapy, one usually gives the maximum tolerated dose. And the
timing is important, because when topotecan is used as chemotherapy one needs
to let the patient recover from toxicity. We propose to give lower doses of
topotecan daily to achieve this effect on HIF-1 in a nontoxic fashion."
Indeed, in an NCI clinical trial, Melillo and colleagues found that
topotecan given this way does not have the toxic effects seen when the drug is
used in massive doses as a chemotherapy.