Exploratory analysis of gene aberrations and chemotherapy response: findings from a real-world database in Japan
Chemotherapy selection relies on tumor tissue of origin. However, since genetic alterations drive tumor behavior, Which factor influences the prediction of response more?
Published in Cancer and Genetics & Genomics
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We retrospectively analyzed 15,474 Japanese patients with solid tumors who underwent comprehensive genomic profiling (CGP) and received cytotoxic chemotherapy. Gene mutations and response were assessed across five chemotherapy classes: platinum-based, alkylating agents, antimetabolites, microtubule inhibitors, and topoisomerase inhibitors.
Genomic alteration data alone did not surpass organ-based models in predicting response. For platinum-based agents, the gene-only model had an AUC of 0.575 versus 0.604 for the organ-only model. A combined gene-organ model yielded an AUC of 0.618 (P < 0.01).Certain gene-organ interactions were associated with improved outcomes. For example, APC-mutated colorectal cancer showed higher ORR and prolonged TNT (hazard ratio, 0.82; 95% CI, 0.73–0.92; P < 0.001) for platinum-based drugs.
We suggeted incorporating both may improve exploratory predictions of chemotherapy response. These exploratory findings require prospective validation before any clinical application.
Division of Gastrointestinal Oncology, Shizuoka Cancer Center
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Oncology
Life Sciences > Health Sciences > Clinical Medicine > Oncology
Chemotherapy
Life Sciences > Biological Sciences > Cancer Biology > Cancer Therapy > Chemotherapy
Gene Mutation
Life Sciences > Biological Sciences > Genetics and Genomics > Molecular Genetics > Gene Mutation
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British Journal of Cancer
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