BRAF mutant colorectal cancer: ErbB2 expression levels as predictive factor for the response to combined BRAF/ErbB inhibitors

• Published in: BMC cancer 2020-02, Vol.20 (1), p.129-129, Article 129
• Main Authors: Miele, Evelina, Abballe, Luana, Spinelli, Gian Paolo, Besharat, Zein Mersini, Catanzaro, Giuseppina, Chiacchiarini, Martina, Vacca, Alessandra, Po, Agnese, Capalbo, Carlo, Ferretti, Elisabetta
• Format: Article
• Language: English
• Subjects: Afatinib; Afatinib - administration & dosage; Analysis; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis; BRAFV600E mutation; Cancer therapies; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Combination drug therapy; Drug dosages; Drug therapy; ErbB protein; ErbB-2 protein; ErbB2; Gene mutation; Genetic aspects; Humans; Immunoglobulins; Investigations; Kinases; Medical prognosis; Metastasis; Molecular Targeted Therapy - methods; Molecular therapy; Monoclonal antibodies; Mutants; Mutation; Panitumumab - administration & dosage; Penicillin; Phenotypes; Proteins; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; Proto-Oncogene Proteins B-raf - genetics; Proto-oncogenes; Raf protein; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - metabolism; Signal Transduction - drug effects; Statistical analysis; Targeted cancer therapy; Vemurafenib; Vemurafenib - administration & dosage
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-020-6586-0

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. 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. Combination strategies with BRAFi and ErbBi achieved a better response in BRAF mutated cells expressing high levels of ErbB2. 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.