Abstract
Our understanding of the complex, adaptive mechanisms of response to targeted therapies in metastatic melanoma is now leading to more effective combination treatments. These include the simultaneous inhibition of signalling pathways and metabolic programmes, as well as epigenetic mechanisms or immunological checkpoints. We review the latest pre-clinical and clinical results of strategies to delay tumor progression through combination approaches, and also highlight some of the problems ahead, including patient stratification, the complexity of targeting adaptive responses, and the management of more severe toxicities that result from double and triple-drug treatments.
Keywords:
Combination treatment; Melanoma; Targeted therapy; Therapeutic resistance.
Copyright © 2020 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Antibodies, Monoclonal, Humanized / administration & dosage
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Antibodies, Monoclonal, Humanized / pharmacology
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents, Immunological / administration & dosage
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Antineoplastic Agents, Immunological / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Epigenesis, Genetic
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Humans
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Melanoma / drug therapy*
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Melanoma / enzymology
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Melanoma / genetics
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Melanoma / immunology
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Molecular Targeted Therapy
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / pharmacology
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Randomized Controlled Trials as Topic
Substances
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Antineoplastic Agents, Immunological
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Protein Kinase Inhibitors