Evaluation of novel targeted anti-melanoma medications in clinical trials

: Early diagnosis of skin cancer (melanoma) can have severe consequences. The treatment options for advanced forms of melanoma were previously restricted, resulting in poor patient recovery. However, due to advancements in medical research, specific approach and therapies have been developed to combat this illness. This study mainly aims to assess the strengths and drawbacks of three generations of targeted medications against melanoma that have been produced during the past decade. Methods: Articles were identified by searching the NCBI-GEO and Elsevier databases using the keyword "melanoma treatment". Results of clinical trial studies investigating melanoma were obtained from the clinicaltrials.gov database. A comprehensive evaluation was conducted on papers, results were categorized, and the strengths and shortcomings of medications in clinical trials were assessed and documented. Results: Targeted anti-BRAFV۶۰۰ drugs and MAPK pathway inhibitors (vemurafenib/cobimetinib, dabrafenib/trametinib, and encorafenib/binimetinib) improved advanced melanoma patients' overall survival and clinical efficacy. To address treatment resistance to anti-BRAF medications, the clinical evaluation of pan-RAF inhibitors has shown that ۱۲% of patients have shown a good response to RAF۲۶۵ therapy, irrespective of the specific RAF mutation. An alternative medication, LY۳۰۰۹۱۲۰, has shown ineffective outcomes in clinical trials conducted on individuals with advanced melanoma, colon cancer, and lung cancer. Therapy with lifirafenib, which targets both the RAF and EGF families, has demonstrated modest efficacy in BRAF-mutated melanoma, while naporafenib is now undergoing clinical trials. Treatment resistance to these medications has been documented, leading to aberrant alterations in ARAF protein and ongoing growth of cancer cells. Multi-drug combination therapy is employed to combat drug resistance. In animal experiments, the concurrent administration of pan-RAF and MEK inhibitors resulted in a decrease in tumor growth, leading to an increase in the functions of killer T cells and a decrease in regulatory T cells. The inclusion of PD-L۱ inhibitors in the combination extended the duration of the response. The study revealed that the administration of pan-RAF inhibitors enhanced the proliferation of tumors harboring KRAS, NRAS, or BRAF mutations when compared to CDK۴/۶ inhibitors. Previous efforts to develop pharmaceuticals against RAS have not achieved success, although they have focused on molecules located downstream of RAS, specifically MEK and ERK. Binimetinib and pimasertib, two anti-MEK medications, elicit a twofold increase in the PFS rate. To address the issue of drug resistance, anti-MEK and anti-ERK medications proved effective, yet, the occurrence of adverse effects significantly escalatedMost recent targeted therapies have targeted the cell cycle, SHP۲, and autophagy with effectiveness. Discussion: Cancer cells have the ability to rapidly acclimate to therapy. Hence, the task of identifying specific and enduring therapies for malignancies characterized by BRAF mutations is very difficult. In general, the outcomes of in vitro studies on melanoma therapy have been positive, and the optimal utilization of these data for melanoma treatment is now in progress.

کلیدواژه ها:

Melanoma ، BRAF ، MEK ، and ERK