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Important players in carcinogenesis as potential targets in cancer therapy: an update.

ABSTRACT: The development of cancer is a problem that has accompanied mankind for years. The growing number of cases, emerging drug resistance, and the need to reduce the serious side effects of pharmacotherapy are forcing scientists to better understand the complex mechanisms responsible for the initiation, promotion, and progression of the disease. This paper discusses the modulation of the particular stages of carcinogenesis by selected physiological factors, including: acetylcholine (ACh), peroxisome proliferator-activated receptors (PPAR), fatty acid-binding proteins (FABPs), Bruton's tyrosine kinase (Btk), aquaporins (AQPs), insulin-like growth factor-2 (IGF-2), and exosomes. Understanding their role may contribute to the development of more effective and safer therapies based on new binding sites.

SUBMITTER: Hermanowicz JM

PROVIDER: S-EPMC7429179 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Important players in carcinogenesis as potential targets in cancer therapy: an update.

Hermanowicz Justyna Magdalena JM Kwiatkowska Iwona I Pawlak Dariusz D

Oncotarget 20200811 32

The development of cancer is a problem that has accompanied mankind for years. The growing number of cases, emerging drug resistance, and the need to reduce the serious side effects of pharmacotherapy are forcing scientists to better understand the complex mechanisms responsible for the initiation, promotion, and progression of the disease. This paper discusses the modulation of the particular stages of carcinogenesis by selected physiological factors, including: acetylcholine (ACh), peroxisome ...[more]

PMID: 32850012

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Project description:Introduction: Cancer is an intricate disorder/dysfunction of cells that can be defined as a genetic heterogeneity in human disease. Therefore, it is characterized by several adaptive complex hallmarks. Among them, the pH dysregulation appears as a symbol of aberrant functions within the tumor microenvironment (TME). In comparison with normal tissues, in the solid tumors, we face with an irregular acidification and alkalinization of the extracellular and intracellular fluids. Methods: In this study, we comprehensively discussed the most recent reports on the hallmarks of solid tumors to provide deep insights upon the molecular machineries involved in the pH dysregulation of solid tumors and their impacts on the initiation and progression of cancer. Results: The dysregulation of pH in solid tumors is fundamentally related to the Warburg effect and hypoxia, leading to expression of a number of molecular machineries, including: NHE1, H+ pump V-ATPase, CA-9, CA-12, MCT-1, GLUT-1. Activation of proton exchangers and transporters (PETs) gives rise to formation of TME. This condition favors the cancer cells to evade from the anoikis and apoptosis, granting them aggressive and metastasis phenotype, as well as resistance to chemotherapy and radiation therapy. This review aimed to discuss the key molecular changes of tumor cells in terms of bio-energetics and cancer metabolism in relation with pH dysregulation. During this phenomenon, the intra- and extracellular metabolites are altered and/or disrupted. Such molecular alterations provide molecular hallmarks for direct targeting of the PETs by potent relevant inhibitors in combination with conventional cancer therapies as ultimate therapy against solid tumors. Conclusion: Taken all, along with other treatment strategies, targeting the key molecular machineries related to intra- and extracellular metabolisms within the TME is proposed as a novel strategy to inhibit or block PETs that are involved in the pH dysregulation of solid tumors.

Dataset Information

Important players in carcinogenesis as potential targets in cancer therapy: an update.

Publications

Important players in carcinogenesis as potential targets in cancer therapy: an update.

Similar Datasets

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