( odel where alternative molecular pathw...)Three Molecular Triggers Threaten Leukemia Patients,Health

odel, where alternative molecular pathways help cancer survive the targeting of one pathway by a drug, is common in cancer, an accompanying editorial in Blood notes.

"This compensatory ability suggests that the use of single "targeted" agents may be suboptimal, a concept that, unfortunately is all too well supported by clinical experience in all malignancies and has broad implications for the entire field of cancer therapeutics," writes Judith Karp, M.D., of the Sidney Kimmel Cancer Center at Johns Hopkins.

"We need to listen carefully to the authors' eloquent plea for a new paradigm in drug development, namely the testing of multiple investigational agents in ways that target complementary molecules and attack the malignant phenotype from multiple angles," Karp concludes.

AML occurs when abnormal blood cells rapidly build up in the bone marrow, interfering with the production of normal blood cells. While chemotherapy often places the disease in remission, it usually comes back. Only about 20 percent of patients are cured with chemotherapy, and another 10 percent are successfully treated with bone marrow transplants.

One of the great successes of cancer treatment has been development of targeted therapy for chronic myelogenous leukemia (CML). The drug Gleevec and its successors inhibit one aberrant protein, increasing the median 5-year survival of CML patients from 50 percent to 90 percent. For AML, that approach won't work. "AML is more complicated, with multiple means of activation," Kornblau says.

The research team looked at activation of three components, one from each pathway, in the leukemic blasts found in newly diagnosed patients. Activation of each component - PKCa, pERK2 and pAKT - had an adverse effect on the patient's prospects that was independent of other traditional prognostic factors. Their cumulative impact was greater than simply adding their individual effects would suggest, the research
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