TY - CHAP
T1 - Melanoma Metabolism
T2 - Cell Survival and Resistance to Therapy
AU - Luís, Rafael
AU - Brito, Cheila
AU - Pojo, Marta
N1 - Funding Information:
The authors would like to thank the support of Liga Portuguesa Contra o Cancro, Núcleo Regional Sul (LPCC-NRS). The authors acknowledge iNOVA4Health – UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement. Sérgio Abreu was responsible for the design of figures.
Publisher Copyright:
© 2020, Springer Nature Switzerland AG.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Immunotherapy
KW - Melanoma
KW - Metabolic profile
KW - Microenvironment
KW - Oncogenic mutations
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=85081043384&partnerID=8YFLogxK
U2 - 10.1007/978-3-030-34025-4_11
DO - 10.1007/978-3-030-34025-4_11
M3 - Chapter
C2 - 32130701
AN - SCOPUS:85081043384
T3 - Advances in Experimental Medicine and Biology
SP - 203
EP - 223
BT - Advances in Experimental Medicine and Biology
PB - Springer
ER -