Journal
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
Volume 180, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.critrevonc.2022.103858
Keywords
Mitochondrial dysfunctions; Onco-targets; Metabolic plasticity Pancreatic cancer
Categories
Funding
- Shaanxi Province Science and Technology Development Plan Project [2022ZDLSF05-05]
- Project of Shaanxi Provincial Administration of Traditional Chinese Medicine [2021-03-ZZ-002]
- Yangzheng Mixture Efficacy Research Project by Shaanxi Buchang Pharmaceutical [20210670]
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This review explores mitochondrial disorders and their targetable molecules in pancreatic cancer, providing new opportunities for therapeutic development, and discusses treatment perspectives based on specific mitochondrial activities.
Pancreatic cancer (PC) is a highly devastating neoplasm due to its irrepressible characteristics and propensity to override the available treatment strategies. Rapid prevalence and enormous severity of this cancer urgently demand the exploration of novel approaches for the development of effective therapeutic measures. Metabolic derangement is one of the hallmarks of cancers which restructures mitochondrial activities and biological pathways. Apart from their bioenergetic and biosynthetic functions, mitochondria are also implicated in a myriad of cellular functions including proliferation, differentiation, apoptosis, senescence, homeostasis, and other cell regulatory mechanisms. It has been noted that PC, like other types of cancers, exploits these activities in favor of tumor growth and survival by inducing mitochondrial dysfunctions such as mitochondrial-DNA mutation, metabolic enzyme modification, ROS generation, mitophagy, evasion of apoptosis, and mitochon-drial biogenesis. During pancreatic carcinogenesis, a large number of onco-factors including Bcl-2 family pro-teins, NF-kappa B, HIFs, NRF2, NOX, MFNs, DRP1, DUSP6, Cyp-D, PARKIN, and others are dysregulated, resulting into reprogramming of metabolic pathways and cellular kinetics. Hence, targeted interventions in these metabolic derangements may present some effective anticancer approaches. The current review gives an insight into various mitochondrial disorders and their targetable molecules in PC which may provide certain novel oppor-tunities in the pursuit of therapeutic development. Furthermore, we have also discussed certain treatment per-spectives in PC based on specific mitochondrial activities.
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