Anatomic Origin No Longer Basis for Cancer Therapy

Traditional cancer therapies, based on different drug regimens for brain, prostate, or ovarian cancer may soon be replaced with therapies that use drugs deemed to be of highest benefit, based on the tumor's pharmacologic profile rather than anatomic origin.

Researchers at the Washington University School of Medicine (St. Louis, MO, USA) compared eight different kinds of cancerous tumors and found that whether the tumor was a breast tumor or a lung tumor did not correlate with how the cancer interacted with a standard anticancer drug. They analyzed 255 samples of eight different cancers, including colon, breast, prostate, ovary, lung, brain, melanoma, and lymphoma, and measured the amounts of specific proteins known to influence the effect of irinotecan, a commonly used anticancer agent.

The protein levels that determine irinotecan's effectiveness were found to be independent of the anatomic origin of the tumor. For example, the colon tumors studied varied widely in the levels of these proteins. This same variation in protein levels held true for all the tumors types examined.

"This study is the first time the pathway for a drug's effect has been analyzed in tumors from different anatomical locations,” said Howard McLeod, Pharm.D,, director of pharmacology at the Siteman Cancer Center at Washington University. "We've shown that drug effect is independent of where the tumor came from in the body. If further studies confirm that a tumor-specific approach is better than the current anatomical emphasis, oncologists may have to stop thinking of themselves as colon cancer or breast cancer specialists and let the cancer tell them which drugs to use for each specific patient.”

The researchers found that, independent of anatomic origin, some tumors had high amounts of irinotecan's cellular target, a protein called TOP1 (topoisomerase [DNA]1), while other tumors had very little. Irinotecan would likely be ineffective in tumors with low TOP1 levels. The researchers also found that tumors varied greatly in amounts of proteins that transport irinotecan into and out of their cells and in the amounts of proteins that break down irinotecan. These variations determine how well irinotecan will work in a particular tumor.

The study is to appear in an upcoming issue of the Journal of Pathology.



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