Academic Journal
MAPK-driven remodeling of mitochondrial dynamics in melanoma: implications for metabolic plasticity and response to targeted therapy.
| Τίτλος: | MAPK-driven remodeling of mitochondrial dynamics in melanoma: implications for metabolic plasticity and response to targeted therapy. |
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| Συγγραφείς: | Prado-Souza LFL; Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil. Electronic address: laura.francisca@ufabc.edu.br., Grabauskas LA; Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil. Electronic address: lorraine.grabauskas@ufabc.edu.br., Chaguri R; Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil. Electronic address: chaguri.r@ufabc.edu.br., Cardoso CD; Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil. Electronic address: caroline.damascena@ufabc.edu.br., Urushima FY; Interdisciplinary Center for Biochemistry Investigation, University of Mogi das Cruzes, SP, Brazil. Electronic address: francinyyuko@gmail.com., Mangini LGR; Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil. Electronic address: luamangini@gmail.com., Ramos VS; Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil. Electronic address: vyctoria.ramos@ufabc.edu.br., Rodrigues T; Center for Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, Brazil. Electronic address: tiago.rodrigues@ufabc.edu.br. |
| Πηγή: | Biochemical pharmacology [Biochem Pharmacol] 2026 Oct; Vol. 252, pp. 118211. Date of Electronic Publication: 2026 Jul 02. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| Ιατρικοί όροι (MeSH): | Melanoma*/metabolism , Melanoma*/drug therapy , Melanoma*/pathology , Mitochondrial Dynamics*/drug effects , Mitochondrial Dynamics*/physiology , Mitogen-Activated Protein Kinases*/metabolism , Mitogen-Activated Protein Kinases*/antagonists & inhibitors , Mitogen-Activated Protein Kinases*/genetics , Antineoplastic Agents*/administration & dosage , Skin Neoplasms*/metabolism , Skin Neoplasms*/drug therapy , MAP Kinase Signaling System*/physiology , MAP Kinase Signaling System*/drug effects, Molecular Targeted Therapy/methods ; Mitochondria/metabolism ; Mitochondria/drug effects ; Protein Kinase Inhibitors/administration & dosage ; Humans ; Animals ; Metabolic Reprogramming |
| Περίληψη: | Melanoma is the most aggressive form of skin cancer due to its high metastatic potential and resistance to therapy. Current treatment strategies include surgical resection for localized disease, as well as targeted therapy with MAPK inhibitors and immunotherapy for advanced stages. However, therapeutic resistance and disease relapse remain major clinical challenges. Activating mutations in components of the mitogen-activated protein kinase (MAPK) pathway, particularly in BRAF and NRAS, are among the most frequent oncogenic events in melanoma, driving tumor initiation and progression through sustained ERK signaling. Mitochondria are dynamic organelles whose morphology is regulated by the balance between fission and fusion. In melanoma cells, MAPK-dependent signaling has been implicated in the regulation of key components of the mitochondrial dynamics machinery, thereby reshaping the mitochondrial network. These structural alterations have functional consequences for cellular metabolism, contributing to metabolic plasticity and enabling tumor cells to switch between glycolytic and oxidative metabolic states in response to environmental stimuli and therapeutic pressures. In this review, we discuss current evidence linking oncogenic MAPK signaling to the control of mitochondrial dynamics in melanoma and examine how these processes contribute to metabolic reprogramming. We further explore how mitochondrial remodeling influences therapeutic response and resistance, particularly in the context of MAPK pathway inhibition. Finally, we highlight mitochondrial dynamics as key regulators of metabolic plasticity and as promising therapeutic targets to improve treatment response in melanoma. (Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tiago Rodrigues reports was provided by Federal University of the ABC. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cancer; Drug resistance; Melanoma; Metabolism; Mitochondria; Targeted therapy |
| Substance Nomenclature: | EC 2.7.11.24 (Mitogen-Activated Protein Kinases) 0 (Antineoplastic Agents) 0 (Protein Kinase Inhibitors) |
| Entry Date(s): | Date Created: 20260702 Date Completed: 20260813 Latest Revision: 20260813 |
| Update Code: | 20260814 |
| DOI: | 10.1016/j.bcp.2026.118211 |
| PMID: | 42392545 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-2968 |
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| DOI: | 10.1016/j.bcp.2026.118211 |