1. BRAF mutant colorectal cancer: ErbB2 expression levels as predictive factor for the response to combined BRAF/ErbB inhibitors.
- Author
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Miele E, Abballe L, Spinelli GP, Besharat ZM, Catanzaro G, Chiacchiarini M, Vacca A, Po A, Capalbo C, and Ferretti E
- Subjects
- Afatinib administration & dosage, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Colorectal Neoplasms pathology, Humans, Molecular Targeted Therapy methods, Panitumumab administration & dosage, Receptor, ErbB-2 metabolism, Vemurafenib administration & dosage, Antineoplastic Combined Chemotherapy Protocols pharmacology, Colorectal Neoplasms drug therapy, Mutation, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Proto-Oncogene Proteins B-raf genetics, Receptor, ErbB-2 antagonists & inhibitors, Signal Transduction drug effects
- Abstract
Background: Colorectal cancer (CRC) is a heterogeneous disease with a complex biology and a wide number of altered genes such as BRAF, KRAS and PIK3CA. Advances with new-targeted therapies have been achieved and available treating options have prolonged patient's survival. However, BRAF-mutated CRC patients remain unresponsive to available therapies with RAF inhibitors (RAFi) alone or combined with ErbB inhibitors (ErbBi). These unmet needs require further exploitation of oncogenic signaling in order to set up individualized treatments., Methods: To this end, we tested the efficacy of single agent or combined treatments using the BRAFi, vemurafenib and two different ErbBi: panitumumab and afatinib in CRC cells characterized by different molecular phenotypes., Results: Combination strategies with BRAFi and ErbBi achieved a better response in BRAF
V600E mutated cells expressing high levels of ErbB2., Conclusions: Our findings support the importance of ErbB2 evaluation in BRAF-mutated CRC patients and its role as a positive predictor factor of response to BRAFi/ErbBi combination.- Published
- 2020
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