This issue of The Oncologist provides the reader with two useful reviews of the new chemotherapeutic agent topotecan, one of a class of topoisomerase I inhibitors that is being studied and incorporated into the treatment of various malignancies. Topotecan was approved for the treatment of refractory ovarian cancer in 1996, and has shown promising activity against a variety of solid tumors, as well as hematologic malignancies. One paper discusses clinical guidelines for managing topotecan-related hematologic toxicities, and centers on data derived from ovarian cancer studies. The other focuses on the role of topotecan in the treatment of small cell lung cancer (SCLC), where it has consistently shown encouraging results and for which definitive trials are now being conducted. As front-line therapy for ovarian cancer and small cell lung cancer is dominated by platinum-based regimens, the dosing guidelines and management issues discussed are pertinent for both tumor types.
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Proc Natl Acad Sci U S A
February 2025
Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114.
Anti-Müllerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this effect is most pronounced with Doxorubicin (DOX). However, DOX toxicity and AMH rescue mechanisms in the ovary have remained unclear. Herein, we characterize the consequences of these treatments in ovarian cell types using scRNAseq.
View Article and Find Full Text PDFCell Transplant
January 2025
Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien.
Leucine-rich repeat-containing G-protein-coupled receptors regulate stem cell activity and tissue homeostasis within female reproductive organs, primarily through their interaction with the Wnt/β-catenin signaling pathway. LGR4-6 are increasingly recognized for their roles in organ development, regeneration, and cancer. This review aims to provide a comprehensive overview of the roles of LGR4-6 in female reproductive organs, highlighting their significance in normal physiology and disease states, specifically in the context of ovarian cancer.
View Article and Find Full Text PDFMol Cancer Ther
January 2025
University of Michigan-Ann Arbor, Ann Arbor, MI, United States.
Up to 90% of high-grade serous ovarian cancer (HGSC) patients will develop resistance to platinum-based chemotherapy, posing substantial therapeutic challenges due to a lack of universally druggable targets. Leveraging BenevolentAI's AI-driven approach to target discovery, we screened potential AI-predicted therapeutic targets mapped to unapproved tool compounds in patient-derived 3D models. This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC.
View Article and Find Full Text PDFCancer Pathog Ther
January 2025
Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, IL 60607, USA.
Background: High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of all ovarian cancer-related deaths. Multiple studies have suggested that the fallopian tube epithelium (FTE) serves as the cell of origin of HGSOC. Phosphatase and tensin homolog () is a tumor suppressor and its loss is sufficient to induce numerous tumorigenic changes in FTE, including increased migration, formation of multicellular tumor spheroids (MTSs), and ovarian colonization.
View Article and Find Full Text PDFBJS Open
December 2024
Department of Obstetrics and Gynecology, and Catharina Cancer Institute, Catharina Hospital, Eindhoven, The Netherlands.
Background: Ovarian cancer is the leading cause of death among gynaecological cancers. The identification of the fallopian tube epithelium as the origin of most ovarian cancers introduces a novel prevention strategy by removing the fallopian tubes during an already indicated abdominal surgery for another reason, also known as an opportunistic salpingectomy. This preventive opportunity is evidence based, recommended and established at the time of gynaecologic surgery in many countries worldwide.
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