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Pfizer's Crizontinib Shows Promise

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Researchers at the Dana-Farber Cancer Institute and their colleagues report positive results for Pfizer's crizontinib, a compound the firm is developing for the treatment of ALK-positive inflammatory myofibroblastic tumors, in a New England Journal of Medicine paper published last week. Because "several ALK fusion proteins, including TPM3-ALK found in IMT, induce transformation in cell lines and animal models, a finding that suggests that ALK rearrangement may define a subgroup of IMTs that is sensitive to targeted kinase inhibition," the team writes, they decided to test the efficacy of crizotinib — ATP-competitive inhibitor of the ALK and MET tyrosine kinases — in two patients with IMTs: one who had a rearrangement in the ALK gene on chromosome 2p23, and one who did not. Post-crizotinib treatment, the former patient's tumors showed shrinking, while the latter patient's tumors showed no improvement, the team reports. Based on these test cases, the Dana-Farber team suggests that signal transduction in a subgroup of IMTs is dependent upin ALK-mediated signal transduction. In noting that " crizotinib has also shown striking clinical activity in non-small-cell lung cancers with EML4-ALK rearrangements," the authors say that "the use of targeted inhibitors to disrupt mutant signaling pathways that cancers require for continued growth has resulted in substantial progress in cancer treatment."

HT: Robert Langreth at Forbes' Treatments