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Updated: Dec 27, 2025
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Melanoma Metabolism: Cell Survival and Resistance to Therapy
Rafael Luís1, Cheila Brito1, Marta Pojo1
1Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E, Lisbon, Portugal.
Abstract:
Cutaneous melanoma is one of the most aggressive types of cancer, presenting the highest potential to form metastases, both locally and distally, which are associated with high death rates of melanoma patients. A high somatic mutation burden is characteristic of these tumours, with most common oncogenic mutations occurring in the BRAF, NRAS and NF1 genes. These intrinsic oncogenic pathways contribute to the metabolic switch between glycolysis and oxidative phosphorylation metabolisms of melanoma, facilitating tumour progression and resulting in a high plasticity and adaptability to unfavourable conditions. Moreover, melanoma microenvironment can influence its own metabolism and reprogram several immune cell subset functions, enabling melanoma to evade the immune system. The knowledge of the biology, molecular alterations and microenvironment of melanoma has led to the development of new targeted therapies and the improvement of patient care. In this work, we reviewed the impact of melanoma metabolism in the resistance to BRAF and MEK inhibitors and immunotherapies, emphasizing the requirement to evaluate metabolic alterations upon development of novel therapeutic approaches. Here we summarized the current understanding of the impact of metabolic processes in melanomagenesis, metastasis and microenvironment, as well as the involvement of metabolic pathways in the immune modulation and resistance to targeted and immunocheckpoint therapies.
Insights
Melanoma metabolism fuels tumor growth, metastasis, and resistance to targeted therapies and immunotherapies. Understanding these metabolic pathways is crucial for developing effective melanoma treatments.
Area of Science:
- Oncology
- Cancer Metabolism
- Immunology
Background:
- Cutaneous melanoma is an aggressive cancer with high metastatic potential and mortality.
- Melanoma exhibits a high somatic mutation burden, often involving BRAF, NRAS, and NF1 genes.
- Tumor metabolism influences melanoma progression, plasticity, and immune evasion.
Purpose of the Study:
- To review the impact of melanoma metabolism on resistance to BRAF/MEK inhibitors and immunotherapies.
- To highlight the necessity of evaluating metabolic alterations in novel therapeutic strategies.
- To summarize current knowledge on metabolic processes in melanoma development, metastasis, and immune modulation.
Main Methods:
- Literature review of melanoma biology, molecular alterations, and microenvironment.
- Analysis of metabolic pathways involved in melanomagenesis and metastasis.
- Examination of metabolic influence on immune cell function and therapeutic resistance.
Main Results:
- Melanoma metabolism drives tumor progression and adaptability.
- The tumor microenvironment significantly impacts melanoma metabolism and immune evasion.
- Metabolic reprogramming is implicated in resistance to targeted therapies and immunotherapies.
Conclusions:
- Metabolic pathways are critical players in melanoma progression, metastasis, and immune evasion.
- Targeting metabolic alterations holds promise for overcoming therapeutic resistance in melanoma.
- A comprehensive understanding of melanoma metabolism is essential for advancing patient care and treatment strategies.
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