Cancer Drug Response Linked to Transcript Isoform Markers

NEW YORK (GenomeWeb) – A Canadian research team has garnered new evidence supporting the notion that the expression of certain transcript isoforms might offer clues to cancer drug response.

The researchers used a new meta-analysis framework to search for splicing isoforms tied to drug response in cell lines assessed for two large pharmacogenomic studies, and looking at more than a dozen cancer drugs. The results, appearing online today in Nature Communications, identified individual transcript isoforms that corresponded to breast cancer cell response to lapatinib, erlotinib, AZD6244, and paclitaxel.

“We validated four isoform-based biomarkers predictive of responses to lapatinib, erlotinib, AZD6244 (MEK inhibitor), and paclitaxel, indicating that isoforms constitute a promising new class of biomarkers for cytotoxic and targeted anticancer therapies,” corresponding author Benjamin Haibe-Kains, a researcher affiliated with the Princess Margaret Cancer Centre, the University of Toronto, and the Ontario Institute of Cancer Research, and his co-authors wrote.

The team’s analysis centered on data from the Broad Institute’s Cancer Cell Line Encyclopedia (CCLE) and the Genomics of Drug Sensitivity in Cancer (GDSC) from the Wellcome Trust Sanger Institute and the Massachusetts General Hospital Cancer Center. By bringing together pan-cancer RNA sequence profiles for more than 1,800 cancer cell lines characterized

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