Abstract
The identification of the fundamental role of apoptosis in the growth balance and normal homeostasis against cell proliferation led to the recognition of its loss contributing to tumorigenesis. The mechanistic significance of reinstating apoptosis signaling towards selective targeting of malignant cells heavily exploits the caspase family of death-inducing molecules as a powerful therapeutic platform for the development of potent anticancer strategies. Some apoptosis inhibitors induce caspase expression and activity in preclinical models and clinical trials by targeting both the intrinsic and extrinsic apoptotic pathways and restoring the apoptotic capacity in human tumors. Furthermore, up-regulation of caspases emerges as a sensitizing mechanism for tumors exhibiting therapeutic resistance to radiation and adjuvant chemotherapy. This review provides a comprehensive discussion of the functional involvement of caspases in apoptosis control and the current understanding of reactivating caspase-mediated apoptosis signaling towards effective therapeutic modalities in cancer treatment.
About the authors
Patrick Hensley is a medical student at the University of Kentucky College of Medicine. He earned a Bachelor of Science degree from Miami University, Oxford, Ohio in 2010. Patrick is currently completing a one year fellowship in the Department of Pathology where he is refining his interests in surgical and molecular oncology. Patrick has spent three years studying novel therapeutics for the treatment of advanced-stage prostate cancer and will pursue residency training in urologic oncology and pathology.
Murli Mishra is a 2nd year graduate student at Graduate Center for Toxicology, College of Medicine, University of Kentucky. He completed his MS (Pharm) with major Regulatory Toxicology from National Institute of Pharmaceutical Education & Research (NIPER), Mohali, India. He completed his bachelor degree in Pharmacy from Poona College of Pharmacy, Bharati Vidyapeeth University, Pune, India. His long term goal is to become a researcher and explore molecular toxicology and cancer biology.
Dr. Natasha Kyprianou is a Professor of Urology, Molecular Biochemistry, Pathology and Toxicology and holds the James F. Hardymon Chair in Urology Research at the University of Kentucky College of Medicine, Lexington, Kentucky. She received her undergraduate and medical school education at the University of London and the University of Leeds, and completed her doctoral studies at the University of Wales College of Medicine in the United Kingdom. Dr. Kyprianou completed fellowships in Molecular Oncology at Johns Hopkins University School of Medicine and in Molecular Biology at the Imperial Cancer Research Fund in London, England. Her research interests focus on the deregulation of apoptosis and growth factor signaling pathways in urologic malignancies and development of molecular therapeutics (via tumor selective apoptosis-targeting) for castration-resistant prostate tumors and novel biomarkers of prostate and bladder cancer metastasis.
This study was supported by the James F. Hardymon Endowment and a University of Kentucky College of Medicine Clinical and Translational Training Fellowship. The authors acknowledge support by a grant from the National Institutes of Health, R01-GRANT00491815, and by the National Center for Research Resources and the National Center for Advancing Translational Sciences, UL1RR033173.
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