Small Molecule B-RAF Inhibitors as Anti-Cancer Therapeutics: Advances in Discovery, Development, and Mechanistic Insights

Authors

Yamile Abuchard Anaya, The University of Texas Rio Grande ValleyFollow
Ricardo Pequeno Bracho, The University of Texas Rio Grande ValleyFollow
Subhash Chauhan, The University of Texas Rio Grande ValleyFollow
Manish K. Tripathi, The University of Texas Rio Grande ValleyFollow
Debasish Bandyopadhyay, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

3-16-2025

Abstract

B-RAF is a serine/threonine kinase that plays a crucial role in the MAPK signaling pathway, regulating cell proliferation and survival. Mutations in B-RAF, particularly V600E, are associated with several malignancies, including melanoma, colorectal cancer, and non-small cell lung cancer, making it a key therapeutic target. The development of B-RAF inhibitors, such as Vemurafenib, Dabrafenib, and second-generation inhibitors like Encorafenib, has led to significant advancements in targeted cancer therapy. However, acquired resistance, driven by MAPK pathway reactivation, RAF dimerization, and alternative signaling pathways, remains a major challenge. This review explores the molecular mechanisms of B-RAF inhibitors, their therapeutic efficacy, and resistance mechanisms, emphasizing the importance of combination strategies to enhance treatment outcomes. The current standard of care involves B-RAF and MEK inhibitors, with additional therapies such as EGFR inhibitors and immune checkpoint blockades showing potential in overcoming resistance. Emerging pan-RAF and brain-penetrant inhibitors offer new opportunities for treating refractory cancers, while precision medicine approaches, including genomic profiling and liquid biopsies, are shaping the future of B-RAF-targeted therapy.

Comments

© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Recommended Citation

Anaya, Y. A., Bracho, R. P., Chauhan, S. C., Tripathi, M. K., & Bandyopadhyay, D. (2025). Small Molecule B-RAF Inhibitors as Anti-Cancer Therapeutics: Advances in Discovery, Development, and Mechanistic Insights. International journal of molecular sciences, 26(6), 2676. https://doi.org/10.3390/ijms26062676

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

International Journal of Molecular Sciences

DOI

10.3390/ijms26062676

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology