The BRAF inhibitor, vemurafenib, has demonstrated improved progression-free and overall survival compared with chemotherapy in a randomized trial, and represents a new standard of care in patients with advanced melanoma harboring a BRAF-V600 mutation. A BRAF-V600 mutation is identified in approximately half of patients with cutaneous melanoma, and is unequivocally a biomarker predictive of profound clinical benefit for these patients. However, acquired vemurafenib resistance is a major clinical challenge and therapy is not yet curative. A substantial body of translational research has been performed alongside clinical trials of vemurafenib, providing key insights into the molecular basis of response and resistance. This review summarizes the development of vemurafenib for the treatment of BRAF-V600 mutant melanoma and discusses how knowledge of critical signaling pathways will be applied for its optimal clinical use in future.
The cyclin D1-Cyclin-Dependent Kinases 4 and 6 (CDK4/6) complex is crucial for the development of melanoma. We previously demonstrated that targeting CDK4/6 using small molecule inhibitors (CDK4/6i) suppresses Braf melanoma growth in vitro and in vivo through induction of cellular senescence. However, clinical trials investigating CDK4/6i in melanoma have not yielded successful outcomes, underscoring the necessity to enhance the therapeutic efficacy of CDK4/6i.
Thyroid cancer (TC) being the common endocrine malignancy is glooming steadily due to its poor prognosis. The treatment strategies of surgery, radiotherapy, and conventional chemotherapy are providing unsatisfactory output. However, combination therapy can negotiate the worse prognosis to the better, where chemoradiotherapy, radiotherapy with surgery, or dual chemotherapeutic drugs are being glorified.
Background/objectives: Drug resistance poses a substantial clinical challenge in melanoma treatment, yet the underlying mechanism remains elusive. Here, we report the novel role of laminB1, a nuclear structure protein, in regulating the response of BRAF-mutated melanoma cells to vemurafenib.
Results: Our analysis of clinical samples and existing databases highlights the tight correlation between the laminB1 expression level and melanoma progression and prognosis.
BRAF and MEK inhibitor (BRAFi + MEKi) therapy has improved the treatment of solid tumors with BRAF mutation. However, their neurologic adverse events (nAEs) have been largely unexplored. This study aimed to provide clinicians with more updated knowledge on nAEs associated with BRAFi + MEKi therapy in patients with malignant melanoma compared with nonmelanoma cancers.
Melanoma, a highly aggressive form of skin cancer, poses a significant global health burden, with 331,647 new cases and 58,645 deaths reported in 2022. The development of melanoma is influenced by various factors, including sunlight exposure and BRAF mutations that activate the MAPK/ERK pathway. The introduction of BRAF and MEK inhibitors has revolutionized the treatment landscape for melanoma patients.
