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Updated: Feb 12, 2026
Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
Published on: September 8, 2021
Recent developments and obstacles in the treatment of melanoma with BRAF and MEK inhibitors
Mohd Wahid1, Arshad Jawed1, Raju K Mandal1
1Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, 45142, Saudi Arabia.
Abstract:
Metastatic melanoma is a least common form of cancer as it accounts only for 1% of all cancer cases. But, it is most deadly in nature and is haunting mankind for long emotionally as well as economically. The sites for the onset of the disease are pigment-producing cells of the skin, mucosa, eye etc. It has the potential to spread other sites like subcutaneous tissue, lymph nodes, lungs, liver, bone and brain. The United States Food & Drug Administration has approved various drug molecules from time to time. The molecules (Dabrafenib-BRAF inhibitor and Trametinib-MEK inhibitor) have proved their credentials alone and in combination as well. These molecules have demonstrated good results for various end points like median progression free survival, overall survival, objective response etc. The median progression free survival for patients using dabrafenib and trametinib were 5.1 and 4.8 months, respectively (administered singly). It has increased to 11.4 months in the combination treatment "dabrafenib + trametinib", which is approximately 104% and 138% greater than dabrafenib and trametinib treated groups alone. Similarly, the overall survival rate and objective response rate for the patients administered with "dabrafenib + trametinib" have been increased by 72% 64%, respectively. All these increments in these parameters were for a short period of time as the molecules were unable to withstand the pressure of resistance developed in the patients. So, the current review suggests the use of BRAF and MEK inhibitors as intermittent therapy along with heat shock protein 90 (HSP90) molecules.
Insights
Metastatic melanoma, though rare, is a deadly cancer. BRAF and MEK inhibitors show promise, but resistance limits their use. Intermittent therapy with HSP90 inhibitors may overcome this. Keywords: metastatic melanoma, BRAF inhibitors, MEK inhibitors, HSP90.
Area of Science:
- Oncology
- Cancer Research
- Pharmacology
Background:
- Metastatic melanoma is a rare but aggressive cancer originating in pigment-producing cells.
- It has a high potential to metastasize to distant organs, significantly impacting patient prognosis.
- Current treatments include targeted therapies like BRAF and MEK inhibitors, approved by the FDA.
Purpose of the Study:
- To evaluate the efficacy of BRAF inhibitors (Dabrafenib) and MEK inhibitors (Trametinib) in treating metastatic melanoma.
- To analyze the impact of combination therapy versus monotherapy on progression-free survival and overall survival.
- To explore novel therapeutic strategies to overcome drug resistance in metastatic melanoma.
Main Methods:
- Review of clinical data on Dabrafenib and Trametinib, both as single agents and in combination.
- Analysis of key endpoints including median progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).
- Exploration of resistance mechanisms and potential synergistic agents.
Main Results:
- Monotherapy with Dabrafenib and Trametinib showed median PFS of 5.1 and 4.8 months, respectively.
- Combination therapy (Dabrafenib + Trametinib) significantly improved median PFS to 11.4 months (104-138% increase).
- Combination therapy also increased OS by 72% and ORR by 64%, but efficacy was limited by acquired resistance.
Conclusions:
- BRAF and MEK inhibitors offer significant survival benefits in metastatic melanoma, particularly in combination.
- Acquired resistance remains a major challenge, limiting long-term efficacy of current targeted therapies.
- Intermittent therapy strategies combined with heat shock protein 90 (HSP90) inhibitors are proposed to overcome resistance and improve outcomes.
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