BRAF V600E in cancer: Exploring structural complexities, mutation profiles, and pathway dysregulation.

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Tác giả: Jayhind Bharti, Ashish Ranjan Dwivedi, Priyadharshini Gogu, Pradeep Kumar, Sarvesh Kumar Pandey, Prateek Pathak, Ankit Kumar Singh, Amita Verma, Jagat Pal Yadav

Ngôn ngữ: eng

Ký hiệu phân loại: 973.928 Administration of George Bush, 1989-1993

Thông tin xuất bản: United States : Experimental cell research , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 468169

BRAF, a fundamental component of cellular signaling pathways regulating growth and survival, is frequently mutated in cancer development. Among entire BRAF mutations, the V600E substitution stands out as a dominant alteration in various malignancies, including melanoma, colorectal cancer, and thyroid cancer. Understanding the structural differences between wild-type BRAF and BRAFV600E is crucial for elucidating the molecular mechanisms underpinnings tumorigenesis and identifying dysregulation associated with the same. V600E mutation results in a constitutively active kinase domain, leading to dysregulated downstream signaling independent of extracellular stimuli. This sustained activation promotes cell proliferation, survival, angiogenesis, and hallmark features of the cancer cells. The study describes three distinct classes of BRAF mutations where Class 1 mutations predominantly involve point mutations within the BRAF gene, while Class 2 encompasses in-frame insertions and deletions, and Class 3 comprises gene fusions with large-scale chromosomal rearrangements. Further, we have discussed dysregulated pathways associated with mutation of BRAFV600E, which includes MAPK/ERK, PI3K/AKT/mTOR, TP53, DNA damage response, and WNT/β-Catenin from schematic representation. In the current review, we have shown how these dysregulated pathways play pivotal roles in tumorigenesis, tumor progression in BRAF-mutant cancers and highlighted the critical role of BRAF dysregulation in cancer development followed by its therapeutic implications of targeting dysregulated pathways in BRAF-driven malignancies.
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