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BRAF mutant colorectal cancer: ErbB2 expression levels as predictive factor for the response to combined BRAF/ErbB inhibitors.
- Source :
-
BMC cancer [BMC Cancer] 2020 Feb 17; Vol. 20 (1), pp. 129. Date of Electronic Publication: 2020 Feb 17. - Publication Year :
- 2020
-
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.<br />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.<br />Results: Combination strategies with BRAFi and ErbBi achieved a better response in BRAF <superscript>V600E</superscript> mutated cells expressing high levels of ErbB2.<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 32066410
- Full Text :
- https://doi.org/10.1186/s12885-020-6586-0