Introduction: The management of patients with BRAF-mutated advanced melanoma who are undergoing targeted therapy with MEK inhibitors can be complicated by the co-administration of multiple medications, which can give rise to drug-drug interactions of clinical significance.
Covered Areas: Our review presents a comprehensive analysis of the pharmacokinetic and pharmacodynamic interactions of the three approved for advanced melanoma MEK inhibitor drugs - binimetinib, cobimetinib, and trametinib. MEDLINE (PubMed) was utilized for the literature search, comprising clinical studies, observational studies, and preclinical research. The review discusses the impact of these interactions on efficacy and safety of the treatments and differentiates between interactions supported by pharmacokinetic or pharmacodynamic mechanisms, those encountered in clinical practice, and those observed in preclinical studies.
Expert Opinion: Physicians should be aware about potential benefits, but also increased toxicity caused by drug interactions between MEK inhibitors and other drugs in the management of patients with metastatic melanoma.
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http://dx.doi.org/10.1080/17425255.2023.2255519 | DOI Listing |
Acta Neuropathol Commun
January 2025
Department of Neuro-Oncology, Columbia University Irving Medical Center, 710 W. 168th Street, New York, NY, 10032, USA.
Glioblastoma (GBM) classification involves a combination of histological and molecular signatures including IDH1/2 mutation, TERT promoter mutation, and EGFR amplification. Non-canonical mutations such as BRAF, found in 1-2% of GBMs, activate the MEK-ERK signaling pathway. This mutation can be targeted by small molecule inhibitors, offering therapeutic potential for GBM.
View Article and Find Full Text PDFMelanoma Manag
December 2024
Department of Medical-Surgical Sciences and Biotechnologies, Dermatology Unit "Daniele Innocenzi", Sapienza University of Rome, Latina, Italy.
Aims: In treating patients with melanoma, the order in which therapy is administered, choosing between targeted therapy and immune checkpoint inhibition, has garnered growing interest.
Patients And Methods: We conducted a retrospective, real-world analysis of patients with advanced melanoma undergoing immunotherapy or targeted therapy as first-line at a single center.
Results: A total of 88 patients diagnosed with melanoma were identified.
Sci Rep
January 2025
Division of Medical Oncology, Marmara University School of Medicine, Istanbul, Turkey.
Management of melanoma has changed significantly with the discovery of targeted therapies and immune checkpoint inhibitors (ICI). Our aim in the study is to determine which treatment alternatives, specifically dabrafenib plus trametinib and ICIs, are effective in adjuvant therapy and which treatment is effective as first-line metastatic therapy. This retrospective, multicenter study included 120 patients diagnosed with stage IIIB-IIID melanoma receiving both adjuvant and first-line metastatic treatment between 2007 and 2023.
View Article and Find Full Text PDFJ Recept Signal Transduct Res
January 2025
Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Lysyl oxidase (LOX), a copper-containing secretory oxidase, plays a key role in the regulation of extracellular stiffness through cross-linking with collagen and elastin. Among the LOX family of enzymes, LOX-like 4 (LOXL4) exhibits pro-tumor and anti-tumor properties; therefore, the functional role of LOXL4 in tumor progression is still under investigation. Here, we first determined that transforming growth factor-β1 (TGF-β1) significantly decreased LOXL4 expression in human breast cancer MDA-MB-231 cells, which suggested that decreased LOXL4 may participate in tumor progression.
View Article and Find Full Text PDFMolecules
January 2025
Cancer Microenvironment Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang-si 10408, Republic of Korea.
As a scaffolding protein, Raf kinase binding protein (RKIP) is involved in a variety of cellular pathways, including the Raf-MEK-ERK-cascade. It acts as a negative regulator by binding to its partners, making it an attractive target in the development of therapeutic strategies for cancer. Despite its structural stability as a monomer, RKIP may form a dimer, resulting in the switching of binding partners.
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