Intratumoral heterogeneity linked to chemotherapy resistance in small-cell lung cancer

Intratumoral heterogeneity linked to chemotherapy resistance in small-cell lung cancer

Reviewed by Kate Anderton, B.Sc. (Editor) Feb 17 2020 Small cell lung cancer (SCLC) accounts for 14% of all lung cancers and is often rapidly resistant to chemotherapy, resulting in poor clinical outcomes. Treatment has changed little for decades, but a study at The University of Texas MD Anderson Cancer Center found that chemotherapy results in increased heterogeneity within the tumor, leading to the evolution of multiple resistance mechanisms. The research team, led by Lauren Averett Byers, M.D., associate professor of Thoracic/Head & Neck Medical Oncology, published their findings today in Nature Cancer. Early results were presented at the American Association for Cancer Research Annual Meeting 2018 in Chicago. There have been few therapeutic advances in the past 30 years, and platinum-based chemotherapy remains the backbone of the standard of care. As a result, five-year survival is less than 7% across all stages. Most patients respond well to platinum chemotherapy initially, but relapse within a few months. There are no highly effective second-line therapies when the tumor recurs." Lauren Averett Byers, M.D., associate professor of Thoracic/Head & Neck Medical Oncology The team found that after treatment, SCLC tumors rapidly evolve. Before treatment, SCLC is largely homogenous, with the same type of cells found throughout the tumor. Within weeks to months of treatment, many new and different types of cells appear; this diversity within the tumor is called intratumoral heterogeneity. "Because you end up with a cancer that has multiple resistance mechanisms turned on at the same time in different cells, the cancer becomes much harder to treat," Byers said. "Some cells might be resistant through one mechanism or pathway, and other cells might be resistant through a different one. Treatment targeting one type of resistance will only kill a subset of cancer cells." A novel method One challenge in studying why and how SCLC chemoresistance occurs is due to the fact that biopsy or surgery isn't required to confirm cancer recurrence for most patients. This leaves investigators with few SCLC samples with which to conduct genomic and biomarker analyses of drug-resistant tumors. Related Stories



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