Decades after their introduction into the clinic, cytotoxic chemotherapeutic drugs continue to be the mainstay of cancer patient care. Why chemotherapeutic drugs are effective in some tumors and not others is not fully understood. Ni Chonghaile et al. (see the Perspective by Reed) hypothesized that differences in chemotherapeutic response might be due to pretreatment differences in the readiness of tumor cells to undergo apoptosis (a form of cell death), a measurable property that they call “mitochondrial priming.” Consistent with this idea, patients with highly primed cancers were found to have a superior clinical response to chemotherapy. In vitro manipulations that increased mitochondrial priming in tumor cells enhanced their sensitivity to chemotherapy.
T. Ni Chonghaile, K. A. Sarosiek, T.-T. Vo, J. A. Ryan, A. Tammareddi, V. Del Gaizo Moore, J. Deng, K. C. Anderson, P. Richardson, Y.-T. Tai, C. S. Mitsiades, U. A. Matulonis, R. Drapkin, R. Stone, D. J. DeAngelo, D. J. McConkey, S. E. Sallan, L. Silverman, M. S. Hirsch, D. Ruben Carrasco, A. Letai, Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy. Science 334, 1129–1133 (2011). [Abstract] [Full Text]