Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Delhi Pharmaceutical Sciences and Research University (DPSRU), New Delhi 110017, India.
School of Pharmaceutical Sciences, MVN University, Palwal, Haryana 121105, India.
Cell Signal. 2024 Oct;122:111329. doi: 10.1016/j.cellsig.2024.111329. Epub 2024 Aug 5.
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.
线粒体,传统上被称为细胞的动力源,现在成为影响癌症进展和耐药性的关键信号中心。该综述强调了凋亡信号、DNA 突变、线粒体动力学和代谢在耐药机制发展和癌症进展中的作用。讨论了靶向方法,重点是管理自噬、融合和分裂线粒体,使耐药癌细胞更容易受到传统治疗的影响。此外,代谢重编程可用于有效靶向代谢酶,如 GLUT1、HKII、PDK 和 PKM2,以避免耐药机制。尽管治疗有潜在的可能性,但线粒体的复杂结构及其在肿瘤发展中的微妙作用阻碍了临床转化。提出了新的靶向药物,为克服癌症中的耐药性提供了新的见解。该研究还强调了谷氨酰胺代谢、线粒体呼吸复合物和凋亡途径作为潜在靶点的重要性,以提高针对耐药性癌症的治疗效果。结合互补和基于纳米粒子的技术靶向线粒体已在癌症治疗中显示出令人鼓舞的结果,为减少耐药性和实现针对每个患者独特特征的个体化治疗方案开辟了道路。提出了药物重定位和线粒体药物递送等创新方法,为提高线粒体靶向治疗的疗效提供了途径。这项全面的研究是癌症治疗的重要一步,有可能影响临床实践并改善患者的治疗效果。