Mitochondria as Key Players in Sarcoma Development, Progression and Drug Resistance: From Mechanistic Insights to New Treatment Opportunities
- 1Department of Oncology, University of Torino, Piazza Nizza 44/bis, 10126 Torino, Italy
- 2Molecular Biotechnology Center “Guido Tarone”, Piazza Nizza 44/bis, 10126 Torino, Italy
Abstract
Sarcomas are a heterogeneous group of tumors accounting for 1% and 15% of adult and child cancers, respectively. Because of their high genomic instability, biological heterogeneity and metastatic potential, sarcomas are challenging to treat. Current treatments rely on surgical resection combined with chemotherapy and radiotherapy; however, the outcome remains poor in advanced or recurrent stages. As in many other solid tumors, a growing body of evidence in sarcoma also highlights the central role of metabolic reprogramming in progression and treatment resistance. Mitochondria are key players in bioenergetic processes, redox balance and apoptotic signaling. This review will discuss the latest findings demonstrating that alterations in mitochondrial energetic metabolism, mitochondrial dynamics and mitochondria-dependent pro-apoptotic signaling promote malignant transformation, progression, immune evasion and resistance to treatments in soft-tissue and bone sarcomas. Mitochondrial pleiotropism, however, can unveil new vulnerabilities. Several compounds disrupting mitochondrial respiration, increasing the production of mitochondrial reactive oxygen species, and triggering mitochondrial-dependent apoptosis achieved promising results at a preclinical level as new anti-sarcoma agents, alone or combined with chemotherapy, radiotherapy or immunotherapy. Knowing the multifaceted roles of mitochondria in sarcoma progression and resistance may be the first step toward new treatment tools, noteworthy for future clinical development.
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BibTeX
@article{perin2026mitochondria,
title = {{Mitochondria as Key Players in Sarcoma Development, Progression and Drug Resistance: From Mechanistic Insights to New Treatment Opportunities}},
author = {Martina Perin and Alberto Lipani and Marco Loffa and Alberto Maria Todesco and Joanna Kopecka and Chiara Riganti},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101422},
url = {https://www.mdpi.com/2218-273X/16/10/1422},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mitochondria as Key Players in Sarcoma Development, Progression and Drug Resistance: From Mechanistic Insights to New Treatment Opportunities
AU - Martina Perin
AU - Alberto Lipani
AU - Marco Loffa
AU - Alberto Maria Todesco
AU - Joanna Kopecka
AU - Chiara Riganti
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101422
UR - https://www.mdpi.com/2218-273X/16/10/1422
AB - Sarcomas are a heterogeneous group of tumors accounting for 1% and 15% of adult and child cancers, respectively. Because of their high genomic instability, biological heterogeneity and metastatic potential, sarcomas are challenging to treat. Current treatments rely on surgical resection combined with chemotherapy and radiotherapy; however, the outcome remains poor in advanced or recurrent stages. As in many other solid tumors, a growing body of evidence in sarcoma also highlights the central role of metabolic reprogramming in progression and treatment resistance. Mitochondria are key players in bioenergetic processes, redox balance and apoptotic signaling. This review will discuss the latest findings demonstrating that alterations in mitochondrial energetic metabolism, mitochondrial dynamics and mitochondria-dependent pro-apoptotic signaling promote malignant transformation, progression, immune evasion and resistance to treatments in soft-tissue and bone sarcomas. Mitochondrial pleiotropism, however, can unveil new vulnerabilities. Several compounds disrupting mitochondrial respiration, increasing the production of mitochondrial reactive oxygen species, and triggering mitochondrial-dependent apoptosis achieved promising results at a preclinical level as new anti-sarcoma agents, alone or combined with chemotherapy, radiotherapy or immunotherapy. Knowing the multifaceted roles of mitochondria in sarcoma progression and resistance may be the first step toward new treatment tools, noteworthy for future clinical development.
SN - 2218-273X
ER -