Question ID: WS-86
Submitted by: David Plas
April 7, 2011
Question: Does circadian control of metabolism influence tumor cell response to chemotherapeutics? Background: It is well established in night-shift workers that disruption of circadian rhythms increases risk for developing metabolic disorders and cancers. Other work has reported that tolerability and efficacy of some chemotherapeutic drugs varies in a circadian manner according to the time of administration. As multiple investigators have found that oncogenes control cytotoxic responses in cancer cells in part through the regulation of metabolism, it is possible that circadian regulation of metabolism may also regulate cancer cell responsiveness to cytotoxic stimuli. Feasibility: Advancing methods in metabolomics make it feasible to determine metabolic function in tumors as a function of the diurnal cycle in model organisms. Metabolic function during treatment with chemotherapeutics could then be measured and correlated with cytotoxic responses. Implications for public health: Changing the time of administration of a chemotherapeutic could be an effective method for manipulating cancer cell metabolism to maximize chemotherapeutic response.
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