"This study provides evidence that the pharmacological pathway of a drug is important, with significant treatment implications," says Rochelle M. Long, Ph.D., of the National Institute of General Medical Sciences and program director for the NIH Pharmacogenetics Research Network. "This work is in keeping with an overarching Network theme of selecting therapies tailored for individual patients instead of a one-size-fits-all approach."
The researchers found that, independent of anatomical origin, some tumors had high amounts of irinotecan's cellular target, a protein labeled TOP1, while other tumors had very little. Irinotecan would likely be ineffective in tumors with low TOP1 levels. They also found that tumors varied greatly in the 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.
"Because tumor response can't be predicted from anatomical location, we should start selecting treatments based on what genes and proteins can tell us about how the tumor will respond to a drug," says McLeod, professor of medicine, of genetics, and of molecular biology and pharmacology. "If we rely just on what has clinically been shown to work in some cases for a particular anatomically defined cancer, we may not initially choose the best therapy for the individual patient. And with advanced cancer, a patient may get only one shot at the right therapy -- making the wrong choice could be deadly."
According to McLeod, under current treatment selection methods virtually no chemotherapeutic drug has been successful i
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Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University School of Medicine
19-Apr-2006