Tumor Heterogeneity and Lesion-Specific Response to Targeted Therapy in Colorectal Cancer.

ABSTRACT:

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How genomic heterogeneity associated with acquired resistance to targeted agents affects response to subsequent therapy is unknown. We studied EGFR blockade in colorectal cancer to assess whether tissue and liquid biopsies can be integrated with radiologic imaging to monitor the impact of individual oncogenic alterations on lesion-specific responses. Biopsy of a patient's progressing liver metastasis following prolonged response to cetuximab revealed a MEK1(K57T) mutation as a novel mechanism of acquired resistance. This lesion regressed upon treatment with panitumumab and the MEK inhibitor trametinib. In circulating tumor DNA (ctDNA), mutant MEK1 levels declined with treatment, but a previously unrecognized KRAS(Q61H) mutation was also identified that increased despite

SUBMITTER: Russo M 

PROVIDER: S-EPMC4744519 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature