Stopping Cancer From Rebounding After Treatment

ByABC News
September 10, 2008, 1:56 PM

Sept. 11 -- WEDNESDAY, Sept. 10 (HealthDay News) -- Tumors often rebound rapidly following chemotherapy, and oncologists may now understand why: Blame the body.

They may also have found a new way to prevent that rebound effect, at least in their mouse model.

Robert Kerbel, of the Sunnybrook Health Sciences Centre, Toronto, and the University of Toronto, led an international team of researchers that discovered that some -- but not all -- chemotherapeutic agents damage not only cancerous tissue, but also the blood vessels that supply that tissue with oxygen and nutrients.

That damage, in turn, induces the body to mobilize so-called "circulating endothelial progenitor" (CEP) cells, blood vessel precursors that home to and repopulate the damaged tumor, enabling it to regenerate.

That effect appeared to be mediated by a cellular growth factor called SDF-1alpha. Fortunately, co-administration of drugs that either block SDF-1alpha or directly block blood vessel development appears to blunt that response -- making the chemotherapy regimen more effective.

"We view this as a yin-yang, action-reaction situation," Kerbel said. "The primary action is the effect of the drug on the tumor. The reaction is the host response, which compromises part of the action, and you want to blunt that with an anti-angiogenic drug and/or something targeting this [protein] SDF-1. That's what this paper is all about."

Should these findings be validated in human subjects, they could potentially explain why anti-angiogenic therapies such as bevacizumab (Avastin) work better with some chemotherapeutics (such as paclitaxel, also called Taxol) than others. They may also explain why tumors seem to rebound so rapidly following chemotherapy treatment, as well as offering up a novel drug target (SDF-1) to suppress this effect. On a more practical level, the findings could help researchers decide which combination therapies to test in clinical trials, and which to put on the back burner.

"These data give a potential explanation for why some [drug] combinations have given much better bang for the buck than others," said Dr. Kathy Miller of the Indiana University School of Medicine in Indianapolis, who co-authored an editorial on Kerbel's study.