Significance: Prostate and ovarian cancers are major contributors to cancer-related deaths worldwide. Recently, inflammation and nitrosative stress have been implicated in carcinogenesis, with the overexpression of NOS2 and concomitant release of nitric oxide (NO) associated with cancer initiation and progression. Recent Advances: An increasing body of evidence indicates an association between NOS2 expression and aggressive ovarian cancer. Research also indicates a role for NO in prostate disease pathology and prostate cancer. A therapeutic role for NOS2 inhibition and/or NO drugs exists for the treatment of both ovarian and prostate tumors.
Critical Issues: Herein, we review the key molecular effects associated with NOS2 in ovarian and prostate cancer. NOS2 increases angiogenesis and tumor proliferation and correlates with aggressive type II ovarian tumors. NOS2 expressing tumors are sensitive to cisplatin chemotherapy, and NO may be used to sensitize cisplatin-resistant tumors to chemotherapy. NOS2 is highly expressed in prostate tumors compared to non-neoplastic prostate pathologies. NO may play a role in the development of androgen-independent prostate cancer via s-nitrosylation of the androgen receptor. Moreover, NOS2 inhibitors and NO donor drugs show therapeutic potential in ovarian and prostate cancer as single agents or dual drugs, by either inhibiting the effects of NOS2 or increasing NO levels to induce cytotoxic effects.
Future Directions: NOS2 and NO present new targets for the treatment of ovarian and prostate tumors. Furthermore, understanding NO-related tumor biology in these cancers presents a new means for improved patient stratification to the appropriate treatment regimen. Antioxid. Redox Signal. 26, 1078-1090.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1089/ars.2017.7004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
GnRH Peptide Antagonist: Comparative Analysis of Chemistry and Formulation with Implications for Clinical Safety and Efficacy.
Pharmaceuticals (Basel)
December 2024
College of Pharmacy, University of Illinois, Chicago, IL 60612, USA.
Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems.
View Article and Find Full Text PDFTargeting UGT2B15 and NR1H4 interaction: a novel therapeutic strategy for polycystic ovary syndrome using naftopidil enantiomers.
J Ovarian Res
January 2025
Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China.
Background: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder among women of reproductive age. It is characterized by hyperandrogenism, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) on ultrasound, often accompanied by metabolic disturbances such as insulin resistance and obesity. Current treatments, including oral contraceptives and anti-androgen medications, often yield limited efficacy and undesirable side effects.
View Article and Find Full Text PDFAdvances in Structural Types and Pharmacochemistry of CDK12 Inhibitors.
Med Chem
January 2025
Key Laboratory of Traditional Chinese Medicine Research and Development of Hebei Province, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde 067000, P.R. China.
Cyclin-Dependent Kinase (CDK) 12 is a member of the 20-membered CDK family (CDK1-20) and plays a vital role in regulating gene transcription, mRNA splicing, translation, cell cycle, and repair of DNA damage. CDK12 is an emerging therapeutic target due to its role in regulating the transcription of DNA Damage Response (DDR) genes in Cyclin-Dependent Kinase (CDK). However, the development of selective small molecules targeting CDK12 has been challenging due to the high degree of homology between kinase domains of CDK12 and other transcriptional CDKs, most notably CDK13.
View Article and Find Full Text PDFImplementation of a sexual health clinic in an oncology setting: patient and provider perspectives.
BMC Health Serv Res
January 2025
Division of Urology, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, M5T 2SB, Canada.
Background: Sexual dysfunction is prevalent among cancer survivors, significantly impacting patient and partner quality of life. Despite this, sexual health clinics (SHCs) remain rare in cancer centres across Canada. An innovative clinic was developed at Princess Margaret Cancer Centre in Toronto, Canada to address this significant gap in survivorship care.
View Article and Find Full Text PDFIntegrating BRCA testing into routine prostate cancer care: a multidisciplinary approach by SIUrO and other Italian Scientific Societies.
BMC Cancer
January 2025
Medical and Translational Oncology, Department of Oncology, Azienda Ospedaliera Santa Maria, Viale Tristano Di Joannuccio 1, Terni, 05100, Italy.
Prostate cancer (PCa) ranks among the most prevalent malignancies in men, with notable associations to Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Lynch Syndrome, both linked to germline likely pathogenetic variant/pathogenetic variant (LPV/PV) in genes involved in DNA repair. Among these genes, BRCA2 in PCa patients is the most frequently altered. Despite progresses, challenges in BRCA carriers detection persist, with a quarter of PCa cases lacking family history.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!