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      Drug Repurposing: A New Hope in Drug Discovery for Prostate Cancer

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          Abstract

          Prostate cancer (PCA), the most common cancer in men, accounted for 1.3 million new incidences in 2018. An increase in incidences is an issue of concern that should be addressed. Of all the reported prostate cancers, 85% were detected in stages III and IV, making them difficult to treat. Conventional drugs gradually lose their efficacy due to the developed resistance against them, thus requiring newer therapeutic agents to be used as monotherapy or combination. Recent research regarding treatment options has attained remarkable speed and development. Therefore, in this context, drug repurposing comes into the picture, which is defined as the “investigation of the off-patent, approved and marketed drugs for a novel therapeutic indication” which saves at least 30% of the time and cost, reducing the cost of treatment for patients, which usually runs high in cancer patients. The anticancer property of cardiac glycosides in cancers was tested in the early 1980s. The trend then shifts toward treating prostate cancer by repurposing other cardiovascular drugs. The current review mainly emphasizes the advantageous antiprostate cancer profile of conventional CVS drugs like cardiac glycosides, RAAS inhibitors, statins, heparin, and beta-blockers with underlying mechanisms.

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          Cancer Statistics, 2021

          Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2021)
          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
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            Autonomic nerve development contributes to prostate cancer progression.

            Claire Magnon, Simon J Hall, Juan Lin … (2013)
            Nerves are a common feature of the microenvironment, but their role in tumor growth and progression remains unclear. We found that the formation of autonomic nerve fibers in the prostate gland regulates prostate cancer development and dissemination in mouse models. The early phases of tumor development were prevented by chemical or surgical sympathectomy and by genetic deletion of stromal β2- and β3-adrenergic receptors. Tumors were also infiltrated by parasympathetic cholinergic fibers that promoted cancer dissemination. Cholinergic-induced tumor invasion and metastasis were inhibited by pharmacological blockade or genetic disruption of the stromal type 1 muscarinic receptor, leading to improved survival of the mice. A retrospective blinded analysis of prostate adenocarcinoma specimens from 43 patients revealed that the densities of sympathetic and parasympathetic nerve fibers in tumor and surrounding normal tissue, respectively, were associated with poor clinical outcomes. These findings may lead to novel therapeutic approaches for prostate cancer.
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              Prostate cancer

              Richard J Rebello, Christoph Oing, Karen Knudsen … (2021)
              Prostate cancer is a complex disease that affects millions of men globally, predominantly in high human development index regions. Patients with localized disease at a low to intermediate risk of recurrence generally have a favourable outcome of 99% overall survival for 10 years if the disease is detected and treated at an early stage. Key genetic alterations include fusions of TMPRSS2 with ETS family genes, amplification of the MYC oncogene, deletion and/or mutation of PTEN and TP53 and, in advanced disease, amplification and/or mutation of the androgen receptor (AR). Prostate cancer is usually diagnosed by prostate biopsy prompted by a blood test to measure prostate-specific antigen levels and/or digital rectal examination. Treatment for localized disease includes active surveillance, radical prostatectomy or ablative radiotherapy as curative approaches. Men whose disease relapses after prostatectomy are treated with salvage radiotherapy and/or androgen deprivation therapy (ADT) for local relapse, or with ADT combined with chemotherapy or novel androgen signalling-targeted agents for systemic relapse. Advanced prostate cancer often progresses despite androgen ablation and is then considered castration-resistant and incurable. Current treatment options include AR-targeted agents, chemotherapy, radionuclides and the poly(ADP-ribose) inhibitor olaparib. Current research aims to improve prostate cancer detection, management and outcomes, including understanding the fundamental biology at all stages of the disease.
              Article 0 comments Cited 217 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): ACS Omega
                Journal ID (iso-abbrev): ACS Omega
                Journal ID (publisher-id): ao
                Journal ID (coden): acsodf
                Title: ACS Omega
                Publisher: American Chemical Society
                ISSN (Electronic): 2470-1343
                Publication date (Electronic): 29 December 2022
                Publication date Collection: 10 January 2023
                Volume: 8
                Issue: 1
                Pages: 56-73
                Affiliations
                [& ]Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research , Guwahati 781003, India
                [‡ ]Biomedical Engineering, Indian Institute of Technology (IIT) , Ropar, Punjab 140001, India
                [§ ]Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research , Ahmedabad, Gujarat 382355, India
                [# ]Sandip Institute of Pharmaceutical Sciences, Savitribai Phule Pune University , Nashik, Maharashtra 422213, India
                [7 ]Department of Pharmacology and Toxicology, University of Hail , Hail 81422, Saudi Arabia
                [▲ ]Department of Pharmaceutics, Annasaheb Dange College of B. Pharmacy, Ashta, Shivaji University , Sangli, Maharastra 416301, India
                Author notes
                Author information
                https://orcid.org/0000-0002-0926-2790
                Article
                DOI: 10.1021/acsomega.2c05821
                PMC ID: 9835086
                PubMed ID: 36643505
                SO-VID: 54244449-2e9f-4588-a149-48fc0f3582ad
                Copyright © © 2022 The Authors. Published by American Chemical Society
                License:

                Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works ( https://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 07 September 2022
                Date accepted : 24 November 2022
                Categories
                Subject: Review
                Custom metadata
                document-id-old-9 ao2c05821
                document-id-new-14 ao2c05821
                ccc-price

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