Cancer Therapy May Backfire

Cancer drugs may induce tumor metastasis

(RxWiki News) Tumors grow and spread in one of two ways - by invading nearby resources, or by sending little pieces into the bloodstream to colonize new areas.

A new study suggests that a common therapy to prevent bloodstream colonization may actually backfire.

Researchers looking at therapies, which prevent the growth of new blood vessels in an attempt to starve tumors, may actually raise the chances of tumors sending out pieces into the bloodstream.

It appears that the drugs limit the growth of cell known as pericytes that envelop blood vessels. When pericyte protective coverage is limited, it's easier for the cancer cells to invade the blood vessel.

This effect, however, can be treated with other therapies.

"Ask your oncologist about supplementing your anti-cancer drugs with anti-metastatic therapy."

A team from both Harvard Medical School and the Beth Israel Medical Center launched a four step experiment, first finding that in genetically engineered mice, fewer amounts of pericytes did limit new blood vessel growth as well as stopping more pericytes from growing.

Consequently, tumors spread through the bloodstream at three times the normal rate, even though the original tumor did shrink an average of 30 percent.

Scientists believe that the lowered amounts of oxygen and nutrients delivered to the tumor sent the cells into a panic mode, sending increased amounts of tumor into the blood stream to look for a new home.

As senior author Raghu Kallur, M.D. Ph.D. said,"This suggested to us that without supportive pericytes, the vasculature inside the tumor was becoming weak and leaky—even more so than it already is inside most tumors—and this was reducing the flow of oxygen to the tumor."

In other words, "Cancer cells respond to hypoxia by launching genetic survival programs," Dr. Kallur explained.

Secondary testing found that drugs which stopped angiogenesis - the creation of new blood vessels - limited pericytes growth as well, supporting the conclusions of the first experiment.

Drugs such as Gleevec (imatinib" data-scaytid="20">imatinib) and Sutent (sunitinib) decreased levels of pericytes both in tumors and in normal tissue by 70 percent, but metastasis increased by a factor of three.

The third component of the study found that this effect could be combated by adding additional drugs specifically to suppress metastasis.

This research may indicate that basic scientific research on the fundamentals of cancer is far from the home stretch. "We must go back and audit the tumor and find out which cells play a protective role versus which cells promote growth and aggression," says Dr. Kalluri. "Not everything is black and white. There are some cells inside a tumor that are actually good in certain contexts."

Finally, as the fourth step, the study analyzed the human correlation of the research, examining 130 breast cancer tumors to measure stage, size and pericyte level. These findings were then compared with the prognosis of the patient.

Scientists found that samples with low numbers of pericytes were on average, the most invasive, with distant metastasis common.

Findings were published in the journal Cancer Cell.

The authors of this study did not disclose any financial conflicts of interest.

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Review Date: 
March 10, 2012