title: RADical response puts an exceptional responder in CHKmate: a synthetic lethal curative response to DNA-damaging chemotherapy?
abstract: In this issue of Cancer Discovery, AI-Ahmadie and colleagues identify a somatic mutation in the RAD50 gene as a likely contributing factor to an unusual curative response to systemic combination therapy employing the DNA-damaging agent irinotecan and a checkpoint kinase 1 inhibitor in a patient with recurrent, metastatic small-cell cancer. This study highlights the importance of in-depth analysis of exceptional responders to chemotherapy and targeted therapy in early-phase clinical trials and opens new avenues for developing cancer genome-based combination therapy to improve the efficacy of traditional chemotherapy through synthetically lethal interactions.
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas. gpeng@mdanderson.org.
authors.forename: Guang
authors.initials: G
authors.lastname: Peng
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Woodman
authors.affiliation: Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
mesh_terms: D017766:Acid Anhydride Hydrolases; D064007:Ataxia Telangiectasia Mutated Proteins / Q000172:deficiency*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes