Cell cycle machinery in oncology: A comprehensive review of therapeutic targets

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Cavalu S.; Abdelhamid A.M.; Saber S.; Elmorsy E.A.; Hamad R.S.; Abdel-Reheim M.A.; Yahya G.; Salama M.M.

Journal: FASEB Journal

Publisher: John Wiley and Sons Inc

Publication Date: 7 June 2024

Volume / Issue: Volume 38 / Issue 11

Article No.: e23734

ISSN: 8926638

DOI: 10.1096/fj.202400769R

Scopus: View on Scopus

PubMed: 38847486

Document Type: Review

Access: All Open Access; Hybrid Gold Open Access

Authors and Affiliations

Cavalu S., Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania; Abdelhamid A.M., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Saber S., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Elmorsy E.A., Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraidah, Saudi Arabia, Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Hamad R.S., Biological Sciences Department, College of Science, King Faisal University, Al Ahsa, Saudi Arabia, Central Laboratory, Theodor Bilharz Research Institute, Giza, Egypt; Abdel-Reheim M.A., Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, Saudi Arabia, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni Suef, Egypt; Yahya G., Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Al Sharqia, Egypt; Salama M.M., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt

Abstract

The cell cycle is tightly regulated to ensure controlled cell proliferation. Dysregulation of the cell cycle machinery is a hallmark of cancer that leads to unchecked growth. This review comprehensively analyzes key molecular regulators of the cell cycle and how they contribute to carcinogenesis when mutated or overexpressed. It focuses on cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, checkpoint kinases, and mitotic regulators as therapeutic targets. Promising strategies include CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib for breast cancer treatment. Other possible targets include the anaphase-promoting complex/cyclosome (APC/C), Skp2, p21, and aurora kinase inhibitors. However, challenges with resistance have limited clinical successes so far. Future efforts should focus on combinatorial therapies, next-generation inhibitors, and biomarkers for patient selection. Targeting the cell cycle holds promise but further optimization is necessary to fully exploit it as an anti-cancer strategy across diverse malignancies. © 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

Keywords

CDK; cell cycle; cyclins; mitosis; therapeutic target; Animals; Antineoplastic Agents; Humans; Molecular Targeted Therapy; Neoplasms; Protein Kinase Inhibitors; abemaciclib; anaphase promoting complex; aurora kinase inhibitor; cell cycle protein; cyclin dependent kinase; cyclin dependent kinase inhibitor; cycline; palbociclib; polo like kinase; protein p21; ribociclib; S phase kinase associated protein 2; antineoplastic agent; protein kinase inhibitor; carcinogenesis; drug targeting; G1 phase cell cycle checkpoint; G2 phase cell cycle checkpoint; gene overexpression; human; M phase cell cycle checkpoint; oncology; patient selection; protein function; protein targeting; Review; animal; drug therapy; metabolism; molecularly targeted therapy; neoplasm; pathology; procedures

Citation Information

Scopus Citations: 49

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