Genes that modulate the sensitivity for anti-microtubule drug-mediated chemotherapy.
Spindle poisons/anti-microtubule drugs are established chemotherapy drugs. These drugs primarily target microtubules and mitotic spindles, activate spindle assembly checkpoint (SAC), resulting in caspase-mediated cell death. However, the terminal phenotypes of drug-treated cells are surprisingly heterogeneous ranging from mitotic catastrophe to apparent senescence, suggesting that input from a variety of signaling pathways influence the cell death process. In recent years, studies revealed several signaling pathways that modulate the efficacy of spindle poisons. In this review, we discuss the genes and pathways whose inhibition or overexpression modulates spindle poison sensitivity. These genes cluster to (i) microtubule, microtubule associating proteins (MAPS) and actin cytoskeleton regulators, (ii) the SAC components, (iii) signaling proteins, (iv) chaperones, (v) cell cycle regulators, (vi) proteasome components, (vii) transcription factors and nuclear receptors, and (viii) apoptotic factors. These gene products would be potential targets for drugs to be combined with spindle poisons. Expression status of these genes would also serve as a prognostic marker for spindle poison-mediated chemotherapy. Understanding signaling pathways involved in drug efficacy will aid to rationally develop synergistic chemotherapy strategy.
Yamada
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Department of Medicine, Hematology/Oncology Section, University of Oklahoma Health Sciences Center (OUHSC), Oklahoma City, OK 73104, USA. Hiroshi-yamada@ouhsc.edu
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D003131:Combined Modality Therapy; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D008869:Microtubule-Associated Proteins