Mitochondrial signaling pathways and their role in cancer drug resistance
Ashwani Sharmaa b, Tarun Virmanib c✉, Girish Kumarb d, Anjali Sharmaa b, Reshu Virmanib e, Dalapathi B Gugulothua, Kuldeep Singhf g, Shashi Kiran Misrah, Kamla Pathaki, Nitin Chitranshij k l, Henrique Douglas Melo Coutinhom n✉
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Abstract
Mitochondria, traditionally known as cellular powerhouses, now emerge as critical signaling centers influencing cancer progression and drug resistance. The review highlights the role that apoptotic signaling, DNA mutations, mitochondrial dynamics and metabolism play in the development of resistance mechanisms and the advancement of cancer. Targeted approaches are discussed, with an emphasis on managing mitophagy, fusion, and fission of the mitochondria to make resistant cancer cells more susceptible to traditional treatments. Additionally, metabolic reprogramming can be used to effectively target metabolic enzymes such GLUT1, HKII, PDK, and PKM2 in order to avoid resistance mechanisms. Although there are potential possibilities for therapy, the complex structure of mitochondria and their subtle role in tumor development hamper clinical translation. Novel targeted medicines are put forth, providing fresh insights on combating drug resistance in cancer. The study also emphasizes the significance of glutamine metabolism, mitochondrial respiratory complexes, and apoptotic pathways as potential targets to improve treatment effectiveness against drug-resistant cancers. Combining complementary and nanoparticle-based techniques to target mitochondria has demonstrated encouraging results in the treatment of cancer, opening doors to reduce resistance and enable individualized treatment plans catered to the unique characteristics of each patient. Suggesting innovative approaches such as drug repositioning and mitochondrial drug delivery to enhance the efficacy of mitochondria-targeting therapies, presenting a pathway for advancements in cancer treatment. This thorough investigation is a major step forward in the treatment of cancer and has the potential to influence clinical practice and enhance patient outcomes.
TL;DRThe role that apoptotic signaling, DNA mutations, mitochondrial dynamics and metabolism play in the development of resistance mechanisms and the advancement of cancer is highlighted, and innovative approaches such as drug repositioning and mitochondrial drug delivery are suggested to enhance the efficacy of mitochondria-targeting therapies. (Semantic Scholar)