Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies

Melanoma possesses invasive metastatic growth patterns and is one of the most aggressive types of skin cancer. In 2021, it is estimated that 7180 deaths were attributed to melanoma in the United States alone. Once melanoma metastasizes, traditional therapies are no longer effective. Instead, immunot...

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Bibliographic Details
Published in:Cancers 2022-08, Vol.14 (15), p.3779
Main Authors: Rager, Taylor, Eckburg, Adam, Patel, Meet, Qiu, Rong, Gantiwala, Shahina, Dovalovsky, Katrina, Fan, Kelly, Lam, Katie, Roesler, Claire, Rastogi, Aayush, Gautam, Shruti, Dube, Namrata, Morgan, Bridget, Nasifuzzaman, S M, Ramaswami, Dhruv, Gnanasekar, Varun, Smith, Jeffrey, Merchant, Aftab, Puri, Neelu
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Biomarkers
c-Kit protein
c-Met protein
Clinical trials
FDA approval
Growth patterns
Immunotherapy
Invasiveness
Kinases
Melanoma
Metastases
Metastasis
Mutation
Patients
Pembrolizumab
Prognosis
Protein-tyrosine kinase
Proteins
Response rates
Review
Skin cancer
Toxicity
Tumorigenesis
Vascular endothelial growth factor receptors
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Summary:Melanoma possesses invasive metastatic growth patterns and is one of the most aggressive types of skin cancer. In 2021, it is estimated that 7180 deaths were attributed to melanoma in the United States alone. Once melanoma metastasizes, traditional therapies are no longer effective. Instead, immunotherapies, such as ipilimumab, pembrolizumab, and nivolumab, are the treatment options for malignant melanoma. Several biomarkers involved in tumorigenesis have been identified as potential targets for molecularly targeted melanoma therapy, such as tyrosine kinase inhibitors (TKIs). Unfortunately, melanoma quickly acquires resistance to these molecularly targeted therapies. To bypass resistance, combination treatment with immunotherapies and single or multiple TKIs have been employed and have been shown to improve the prognosis of melanoma patients compared to monotherapy. This review discusses several combination therapies that target melanoma biomarkers, such as BRAF, MEK, RAS, c-KIT, VEGFR, c-MET and PI3K. Several of these regimens are already FDA-approved for treating metastatic melanoma, while others are still in clinical trials. Continued research into the causes of resistance and factors influencing the efficacy of these combination treatments, such as specific mutations in oncogenic proteins, may further improve the effectiveness of combination therapies, providing a better prognosis for melanoma patients.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14153779