BRAF, also known as B-Raf proto-oncogene, encodes a cytoplasmic serine/threonine kinase. It plays a key role in regulating the mitogen-activated protein kinase (MAPK) signal transduction pathway, which is crucial for cell proliferation, differentiation, apoptosis, and senescence [4,5].

BRAF is frequently mutated in many cancers. In melanoma, about 40-50% of cases have BRAF mutations, mostly at codon 600 (e.g., V600E), leading to constitutive activation of the MAPK pathway [1,6]. In colorectal cancer (CRC), BRAF mutation is present in about 10% of patients, associated with poor response to chemotherapy [3]. In non-small-cell lung cancer (NSCLC), BRAF mutations are found in 1%-2% of adenocarcinoma, commonly in never-smokers and women [7]. BRAF inhibitors have shown promise in treating BRAF-mutated cancers, but resistance mechanisms often develop [1,3,8,9]. For example, in melanoma, resistance may occur via reactivation of MAPK through CRAF/COT overexpression [9]. Also, BRAF mutational heterogeneity exists in melanoma, which may affect the indication of BRAF/MEK inhibitors [2].

In conclusion, BRAF is a critical component of the MAPK pathway. Its mutations are associated with the development and progression of multiple cancers, including melanoma, CRC, and NSCLC. Studies on BRAF-mutated cancers, especially those using gene-targeted therapies, have provided insights into the role of BRAF in cancer pathogenesis and potential treatment strategies. Understanding BRAF and its mutations is essential for developing more effective cancer therapies.

References:

1. Castellani, Giorgia, Buccarelli, Mariachiara, Arasi, Maria Beatrice, Lintas, Carla, Tabolacci, Claudio. 2023. BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers. In Cancers, 15, . doi:10.3390/cancers15164026. https://pubmed.ncbi.nlm.nih.gov/37627054/

2. Ito, Takamichi, Tanaka, Yuka, Murata, Maho, Furue, Kazuhisa, Furue, Masutaka. 2021. BRAF Heterogeneity in Melanoma. In Current treatment options in oncology, 22, 20. doi:10.1007/s11864-021-00818-3. https://pubmed.ncbi.nlm.nih.gov/33558987/

3. Aiman, Wajeeha, Ali, Muhammad Ashar, Jumean, Samer, Guron, Gunwant, Shaaban, Hamid. 2023. BRAF Inhibitors in BRAF-Mutated Colorectal Cancer: A Systematic Review. In Journal of clinical medicine, 13, . doi:10.3390/jcm13010113. https://pubmed.ncbi.nlm.nih.gov/38202120/

4. Loo, Eric, Khalili, Parisa, Beuhler, Karen, Siddiqi, Imran, Vasef, Mohammad A. . BRAF V600E Mutation Across Multiple Tumor Types: Correlation Between DNA-based Sequencing and Mutation-specific Immunohistochemistry. In Applied immunohistochemistry & molecular morphology : AIMM, 26, 709-713. doi:10.1097/PAI.0000000000000516. https://pubmed.ncbi.nlm.nih.gov/29271794/

5. Liu, Haotian, Nazmun, Nahar, Hassan, Shafat, Liu, Xinyue, Yang, Jilong. 2020. BRAF mutation and its inhibitors in sarcoma treatment. In Cancer medicine, 9, 4881-4896. doi:10.1002/cam4.3103. https://pubmed.ncbi.nlm.nih.gov/32476297/

6. Pelosi, Elvira, Castelli, Germana, Testa, Ugo. 2024. Braf-Mutant Melanomas: Biology and Therapy. In Current oncology (Toronto, Ont.), 31, 7711-7737. doi:10.3390/curroncol31120568. https://pubmed.ncbi.nlm.nih.gov/39727691/

7. Yan, Ningning, Guo, Sanxing, Zhang, Huixian, Shen, Shujing, Li, Xingya. 2022. BRAF-Mutated Non-Small Cell Lung Cancer: Current Treatment Status and Future Perspective. In Frontiers in oncology, 12, 863043. doi:10.3389/fonc.2022.863043. https://pubmed.ncbi.nlm.nih.gov/35433454/

8. Foth, Mona, McMahon, Martin. 2021. Autophagy Inhibition in BRAF-Driven Cancers. In Cancers, 13, . doi:10.3390/cancers13143498. https://pubmed.ncbi.nlm.nih.gov/34298710/

9. Alqathama, Aljawharah. 2020. BRAF in malignant melanoma progression and metastasis: potentials and challenges. In American journal of cancer research, 10, 1103-1114. doi:. https://pubmed.ncbi.nlm.nih.gov/32368388/