New Strategies for Manipulating Mitochondrial Dynamics in Cancer Therapy

Authors

  • Tolulope Bolarinwa Indepenent Researcher, Indiana, USA Author
  • Opeoluwa Oluwanifemi Akomolafe Independent Researcher, UK Author
  • Irene Sagay-Omonogor Independent Researcher, Maryland, MD, USA Author

DOI:

https://doi.org/10.32628/IJSRCH

Keywords:

Mitochondrial Dynamics, Cancer Therapy, Mitochondrial Fission, Mitochondrial Fusion, Targeted Therapy

Abstract

Mitochondrial dynamics, encompassing fission, fusion, biogenesis, and mitophagy, play critical roles in cancer cell survival and proliferation. Targeting these processes has emerged as a promising therapeutic strategy. Current approaches, including mitochondrial-targeted drugs and inhibitors of key regulatory proteins, have shown potential but face limitations such as off-target effects and resistance. Emerging strategies involve innovative techniques like mitochondrial uncouplers, modulation of calcium homeostasis, and nanotechnology-based delivery systems. Future research aims to develop more selective inhibitors, explore the interplay between mitochondrial dynamics and cellular processes, and enhance targeted delivery systems. These advancements hold significant clinical implications, offering more effective and less toxic cancer treatments, improving the efficacy of existing therapies' efficacy, and enabling personalized approaches. Continued exploration of these strategies promises to advance cancer therapy and improve patient outcomes.

References

Abate, M., Festa, A., Falco, M., Lombardi, A., Luce, A., Grimaldi, A., . . . Caraglia, M. (2020). Mitochondria as playmakers of apoptosis, autophagy and senescence. Paper presented at the Seminars in cell & developmental biology.

Ahmed, A., Trezza, A., Gentile, M., Paccagnini, E., Lupetti, P., Spiga, O., . . . Fusi, F. (2022). The drp-1-mediated mitochondrial fission inhibitor mdivi-1 impacts the function of ion channels and pathways underpinning vascular smooth muscle tone. Biochemical Pharmacology, 203, 115205.

Bosc, C., Saland, E., Bousard, A., Gadaud, N., Sabatier, M., Cognet, G., . . . Aroua, N. (2021). Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia. Nature cancer, 2(11), 1204-1223.

Boulton, D. P., & Caino, M. C. (2022). Mitochondrial fission and fusion in tumor progression to metastasis. Frontiers in Cell and Developmental Biology, 10, 849962.

Chandel, N. S. (2021). Mitochondria. Cold Spring Harbor perspectives in biology, 13(3), a040543.

Chandraprasad, M. S., Dey, A., & Swamy, M. K. (2022). Introduction to cancer and treatment approaches. In Paclitaxel (pp. 1-27): Elsevier.

Chapman, J., Ng, Y. S., & Nicholls, T. J. (2020). The maintenance of mitochondrial DNA integrity and dynamics by mitochondrial membranes. Life, 10(9), 164.

Dai, C.-Q., Guo, Y., & Chu, X.-Y. (2020). Neuropathic pain: the dysfunction of Drp1, mitochondria, and ROS homeostasis. Neurotoxicity Research, 38(3), 553-563.

Du, F., Yang, L.-h., Liu, J., Wang, J., Fan, L., Duangmano, S., . . . Zhong, X. (2023). The role of mitochondria in the resistance of melanoma to PD-1 inhibitors. Journal of Translational Medicine, 21(1), 345.

Eldeeb, M. A., Esmaili, M., Hassan, M., & Ragheb, M. A. (2022). The role of PTEN-L in modulating PINK1-Parkin-mediated mitophagy. Neurotoxicity Research, 40(4), 1103-1114.

Feng, S.-T., Wang, Z.-Z., Yuan, Y.-H., Wang, X.-L., Sun, H.-M., Chen, N.-H., & Zhang, Y. (2020). Dynamin-related protein 1: A protein critical for mitochondrial fission, mitophagy, and neuronal death in Parkinson’s disease. Pharmacological Research, 151, 104553.

Foo, B. J.-A., Eu, J. Q., Hirpara, J. L., & Pervaiz, S. (2021). Interplay between mitochondrial metabolism and cellular redox state dictates cancer cell survival. Oxidative Medicine and Cellular Longevity, 2021(1), 1341604.

Genovese, I., Carinci, M., Modesti, L., Aguiari, G., Pinton, P., & Giorgi, C. (2021). Mitochondria: insights into crucial features to overcome cancer chemoresistance. International Journal of Molecular Sciences, 22(9), 4770.

Ghosh, P., Vidal, C., Dey, S., & Zhang, L. (2020). Mitochondria targeting as an effective strategy for cancer therapy. International Journal of Molecular Sciences, 21(9), 3363.

Grel, H., Woznica, D., Ratajczak, K., Kalwarczyk, E., Anchimowicz, J., Switlik, W., . . . Jakiela, S. (2023). Mitochondrial dynamics in neurodegenerative diseases: unraveling the role of fusion and fission processes. International Journal of Molecular Sciences, 24(17), 13033.

Han, Y. (2021). Chemoresistance and metastatic potential of ovarian cancer cells governed by the tumor microenvironment.서울대학교대학원,

Hsu, C.-C., Peng, D., Cai, Z., & Lin, H.-K. (2022). AMPK signaling and its targeting in cancer progression and treatment. Paper presented at the Seminars in cancer biology.

Huang, Y., Sun, G., Sun, X., Li, F., Zhao, L., Zhong, R., & Peng, Y. (2020). The potential of lonidamine in combination with chemotherapy and physical therapy in cancer treatment. Cancers, 12(11), 3332.

Ippolito, L., Giannoni, E., Chiarugi, P., & Parri, M. (2020). Mitochondrial redox hubs as promising targets for anticancer therapy. Frontiers in Oncology, 10, 256.

Johariya, V., Joshi, A., Malviya, N., & Malviya, S. (2024). Introduction to Cancer. In Medicinal Plants and Cancer Chemoprevention (pp. 1-28): CRC Press.

Kocianova, E., Piatrikova, V., & Golias, T. (2022). Revisiting the Warburg effect with focus on lactate. Cancers, 14(24), 6028.

Kumar, S., Ashraf, R., & CK, A. (2022). Mitochondrial dynamics regulators: implications for therapeutic intervention in cancer. Cell biology and toxicology, 1-30.

Macleod, K. F. (2020). Mitophagy and mitochondrial dysfunction in cancer. Annual Review of Cancer Biology, 4(1), 41-60.

Mao, L., Liu, H., Zhang, R., Deng, Y., Hao, Y., Liao, W., . . . Sun, S. (2021). PINK1/Parkin-mediated mitophagy inhibits warangalone-induced mitochondrial apoptosis in breast cancer cells. Aging (Albany NY), 13(9), 12955.

Moindjie, H., Rodrigues-Ferreira, S., & Nahmias, C. (2021). Mitochondrial metabolism in carcinogenesis and cancer therapy. Cancers, 13(13), 3311.

Passaniti, A., Kim, M. S., Polster, B. M., & Shapiro, P. (2022). Targeting mitochondrial metabolism for metastatic cancer therapy. Molecular carcinogenesis, 61(9), 827-838.

Patergnani, S., Danese, A., Bouhamida, E., Aguiari, G., Previati, M., Pinton, P., & Giorgi, C. (2020). Various aspects of calcium signaling in the regulation of apoptosis, autophagy, cell proliferation, and cancer. International Journal of Molecular Sciences, 21(21), 8323.

Peruzzo, R., Costa, R., Bachmann, M., Leanza, L., & Szabò, I. (2020). Mitochondrial metabolism, contact sites and cellular calcium signaling: implications for tumorigenesis. Cancers, 12(9), 2574.

Poole, L. P., & Macleod, K. F. (2021). Mitophagy in tumorigenesis and metastasis. Cellular and molecular life sciences, 78, 3817-3851.

Praharaj, P. P., Patro, B. S., & Bhutia, S. K. (2022). Dysregulation of mitophagy and mitochondrial homeostasis in cancer stem cells: novel mechanism for anti‐cancer stem cell‐targeted cancer therapy. British Journal of Pharmacology, 179(22), 5015-5035.

Rai, Y., Kumari, N., Singh, S., Kalra, N., Soni, R., & Bhatt, A. N. (2021). Mild mitochondrial uncoupling protects from ionizing radiation induced cell death by attenuating oxidative stress and mitochondrial damage. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1862(1), 148325.

Ramesh, P., & Medema, J. P. (2020). BCL-2 family deregulation in colorectal cancer: potential for BH3 mimetics in therapy. Apoptosis, 25(5), 305-320.

Rodrigues, T., & Ferraz, L. S. (2020). Therapeutic potential of targeting mitochondrial dynamics in cancer. Biochemical Pharmacology, 182, 114282.

Sainero-Alcolado, L., Liaño-Pons, J., Ruiz-Pérez, M. V., & Arsenian-Henriksson, M. (2022). Targeting mitochondrial metabolism for precision medicine in cancer. Cell Death & Differentiation, 29(7), 1304-1317.

Su, Q., Wang, J., Liu, F., & Zhang, Y. (2020). Blocking Parkin/PINK1-mediated mitophagy sensitizes hepatocellular carcinoma cells to sanguinarine-induced mitochondrial apoptosis. Toxicology in Vitro, 66, 104840.

Tayeb, F. (2024). Dysregulation of BCL-2 family proteins in blood neoplasm: therapeutic relevance of antineoplastic agent venetoclax. Exploration of Medicine, 5, 331-350.

Urbano, A. M. (2021). Otto Warburg: The journey towards the seminal discovery of tumor cell bioenergetic reprogramming. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1867(1), 165965.

Wang, X.-L., Feng, S.-T., Wang, Z.-Z., Chen, N.-H., & Zhang, Y. (2021). Role of mitophagy in mitochondrial quality control: Mechanisms and potential implications for neurodegenerative diseases. Pharmacological Research, 165, 105433.

Waseem, M., & Wang, B.-D. (2023). Promising strategy of mPTP modulation in cancer therapy: an emerging progress and future insight. International Journal of Molecular Sciences, 24(6), 5564.

Yang, Y., An, Y., Ren, M., Wang, H., Bai, J., Du, W., & Kong, D. (2023). The mechanisms of action of mitochondrial targeting agents in cancer: inhibiting oxidative phosphorylation and inducing apoptosis. Frontiers in Pharmacology, 14, 1243613.

Zou, G.-P., Yu, C.-X., Shi, S.-L., Li, Q.-G., Wang, X.-H., Qu, X.-H., . . . Jiang, L.-P. (2021). Mitochondrial dynamics mediated by DRP1 and MFN2 contributes to cisplatin chemoresistance in human ovarian cancer SKOV3 cells. Journal of Cancer, 12(24), 7358.

Zunica, E. R. M. (2022). Metabolic Therapeutics for the Treatment of Breast Cancer. Case Western Reserve University,

Downloads

Published

20-12-2024

Issue

Section

Research Articles