Small molecules targeting mitochondria as an innovative approach to cancer therapy

• Published in: Cellular signalling 2024-12, Vol.124, p.111396, Article 111396
• Main Authors: Kamble, Omkar S., Chatterjee, Rana, Abishek, K.G., Chandra, Jyoti, Alsayari, Abdulrhman, Wahab, Shadma, Sahebkar, Amirhossein, Kesharwani, Prashant, Dandela, Rambabu
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; cancer; Humans; Mitocans; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial targeting; Neoplasms - drug therapy; Neoplasms - metabolism; Small Molecule Libraries - chemistry; Small Molecule Libraries - pharmacology; Small Molecule Libraries - therapeutic use; Small molecules
• ISSN: 0898-6568; 1873-3913; 1873-3913
• DOI: 10.1016/j.cellsig.2024.111396

Cellular death evasion is a defining characteristic of human malignancies and a significant contributor to therapeutic inefficacy. As a result of oncogenic inhibition of cell death mechanisms, established therapeutic regimens seems to be ineffective. Mitochondria serve as the cellular powerhouses, but they also function as repositories of self-destructive weaponry. Changes in the structure and activities of mitochondria have been consistently documented in cancer cells. In recent years, there has been an increasing focus on using mitochondria as a targeted approach for treating cancer. Considerable attention has been devoted to the development of delivery systems that selectively aim to deliver small molecules called “mitocans” to mitochondria, with the ultimate goal of modulating the physiology of cancer cells. This review summarizes the rationale and mechanism of mitochondrial targeting with small molecules in the treatment of cancer, and their impact on the mitochondria. This paper provides a concise overview of the reasoning and mechanism behind directing treatment towards mitochondria in cancer therapy, with a particular focus on targeting using small molecules. This review also examines diverse small molecule types within each category as potential therapeutic agents for cancer. •The key role of mitochondria in metabolism, cell survival, and providing energy•Mitochondria is an essential target in the research anti-cancer treatment.•We discussed potent novel small molecules targeting mitochondria for cancer therapy.