MicroRNA 31-3p expression and benefit from anti-EGFR inhibitors in metastatic colorectal cancer patients enrolled in the prospective phase II PROSPECT-C trial.
Darvish Damavandi, M
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PURPOSE: Anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibodies (mABs) are effective in the treatment of metastatic colorectal cancer (mCRC) patients. RAS status and tumour location (sidedness) are predictive markers of patients' response to anti-EGFR mABs. Recently, low microRNA-31-3p expression levels have been correlated with clinical benefit from the anti-EGFR mAb cetuximab. Here we aimed to validate the predictive power of microRNA-31-3p in a prospective cohort of chemo-refractory mCRC patients treated with single agent anti-EGFR mABs. EXPERIMENTAL DESIGN: microRNA-31-3p was tested by in-situ hybridization in ninety-one pre-treatment core biopsies from metastatic deposits of forty-five mCRC patients. Sequential tissue biopsies obtained before treatment, at the time of partial response, and at disease progression were tested to monitor changes in microRNA-31-3p expression over treatment. MicroRNA-31-3p expression, sidedness, and RAS status in pre-treatment cell-free DNA were combined in multivariable regression models to assess the predictive value of each variable alone or in combination. RESULTS: Patients with low microRNA-31-3p expression in pre-treatment biopsies showed better overall response rate, as well as better progression free and overall survival, compared to those with high microRNA-31-3p expression. The prognostic effect of microRNA-31-3p was independent from age, gender and sidedness. No significant changes in the expression of microRNA-31-3p were observed when sequential tissue biopsies were tested in long-term or poor responders to anti-EGFR mABs. MicroRNA-31-3p scores were similar when pre-treatment biopsies were compared with treatment-naïve archival tissues (often primary CRC).Conclusions: Our study validates the role of microRNA-31-3p as potential predictive biomarker of selection for anti-EGF mABs.
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Signal Transduction & Molecular Pharmacology
Gastrointestinal Cancers Clinical Trials
Medicine (RMH Smith Cunningham)
Gastrointestinal Cancer Biology and Genomics
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Clin Cancer Res, 2019