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Review
. 2024 Sep 12;13(18):5409.
doi: 10.3390/jcm13185409.

Advancements and Challenges in Personalized Therapy for BRAF-Mutant Melanoma: A Comprehensive Review

Abdulaziz Shebrain  1 , Omer A Idris  1   2 , Ali Jawad  1 , Tiantian Zhang  3 , Yan Xing  4
Affiliations
Review

Advancements and Challenges in Personalized Therapy for BRAF-Mutant Melanoma: A Comprehensive Review

Abdulaziz Shebrain et al. J Clin Med. .

Abstract

Over the past several decades, advancements in the treatment of BRAF-mutant melanoma have led to the development of BRAF inhibitors, BRAF/MEK inhibitor combinations, anti-PD-1 therapy, and anti-CTLA4 therapy. Although these therapies have shown substantial efficacy in clinical trials, their sustained effectiveness is often challenged by the tumor microenvironment, which is a highly heterogeneous and complex milieu of immunosuppressive cells that affect tumor progression. The era of personalized medicine holds substantial promise for the tailoring of treatments to individual genetic profiles. However, tumor heterogeneity and immune evasion mechanisms contribute to the resistance to immunotherapy. Despite these challenges, tumor-infiltrating lymphocyte (TIL) therapy, as exemplified by lifileucel, has demonstrated notable efficacy against BRAF V600-mutant melanoma. Additionally, early response biomarkers, such as COX-2 and MMP2, along with FDG-PET imaging, offer the potential to improve personalized immunotherapy by predicting patient responses and determining the optimal treatment duration. Future efforts should focus on reducing the T-cell harvesting periods and costs associated with TIL therapy to enhance efficiency and accessibility.

Keywords: BRAF mutation; biomarker discovery; chimeric antigen receptor T-cell therapy; immunotherapy; lifileucel; melanoma; neoantigens; neoplasm heterogeneity; precision medicine; tumor microenvironment; tumor-infiltrating lymphocytes.

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Conflict of interest statement

Omer A. Idris, is affiliated with Malate Inc., a research consulting company that provides research services and mentorship. This affiliation does not present a conflict of interest with respect to the content of this manuscript. The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Components and immunomodulatory effects of the BRAF-mutant melanoma tumor microenvironment (created with BioRender.com). This figure illustrates the complex interplay of immune cells and signaling pathways within the tumor microenvironment of BRAF-mutant melanoma. Key components include CD4+ T cells that enhance anti-tumor activity, macrophages that influence tumor growth and metastasis, myeloid dendritic cells that modulate T-cell responses, and cancer-associated fibroblasts (CAFs) that promote immune evasion. Hematopoietic stem cells and mucosal-associated invariant T cells (MAIT) contribute to shaping the immune landscape, collectively impacting anti-tumor immunity and treatment outcomes.
Figure 2
Figure 2
Visual representation of personalized therapy pathways in BRAF-mutant melanoma.
See this image and copyright information in PMC

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