Colon Cancer Cells Evade Drug Action by Enhancing Drug Metabolism.

ABSTRACT: Colorectal cancer (CRC) is the second most deadly cancer worldwide. One key reason is the failure of therapies that target RAS proteins, which represent approximately 40% of CRC cases. Despite the recent discovery of multiple alternative signalling pathways that contribute to resistance, durable therapies remain an unmet need. Here, we use liquid chromatography/mass spectrometry (LC/MS) analyses on Drosophila CRC tumour models to identify multiple metabolites in the glucuronidation pathway-a toxin clearance pathway-as upregulated in trametinib-resistant RAS/APC/P53 ("RAP") tumours compared to trametinib-sensitive RAS ^G12V tumours. Elevating glucuronidation was sufficient to direct trametinib resistance in RAS ^G12V anima

SUBMITTER: Cong B 

PROVIDER: S-EPMC10769412 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature