Pretreatment Mitochondrial Priming Correlates with Clinical Response to Cytotoxic Chemotherapy

• DOI: 10.1126/science.1206727
• Publication Date: 2011-10-28T02:21:05Z
• Authors: Triona Ni Chonghaile; Kristopher A. Sar...; Thanh-Trang Vo; Jeremy A. Ryan; Anupama Tammareddi; Victoria Del Gaiz...; Jing Deng; Kenneth C. Anderson; Paul Richardson; Yu-Tzu Tai; Constantine S. Mi...; Ursula A. Matulonis; Ronny Drapkin; Richard Stone; Daniel J. DeAngelo; David J. McConkey; Stephen E. Sallan; Lewis Silverman; Michelle S. Hirsch; Daniel Ruben Carr...; Anthony Letai
• Keywords: Priming (agriculture)

Cytotoxic chemotherapy targets elements common to all nucleated human cells, such as DNA and microtubules, yet it selectively kills tumor cells. Here we show that clinical response these drugs correlates with, may be partially governed by, the pretreatment proximity of cell mitochondria apoptotic threshold, a property called mitochondrial priming. We used BH3 profiling measure priming in cells from patients with multiple myeloma, acute myelogenous lymphoblastic leukemia, ovarian cancer. This assay measures peptides derived proapoptotic domains proteins critical for death signaling mitochondria. Patients highly primed cancers exhibited superior chemotherapy. In contrast, chemoresistant normal tissues were poorly primed. Manipulation might enhance efficacy cytotoxic agents.