High-grade serous ovarian cancers account for most ovarian-cancer mortality. Although this disease initially responds well to platinum-based chemotherapy, relapse and progression to chemotherapy resistance are frequently seen. Time to relapse after first-line therapy is a predictor of response to secondary platinum treatment: more than 12 months is associated with high chance of a secondary response, whereas relapses within 6 months generally indicate platinum resistance. In this Personal View we discuss whether patterns of response, relapse, and the development of drug resistance in high-grade serous ovarian cancers are related to distinct underlying molecular and cellular biological characteristics. In particular, we propose that rapid relapse with platinum-resistant disease is due to minor subpopulations of intrinsically resistant cancer cells at presentation.
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http://dx.doi.org/10.1016/S1470-2045(11)70123-1 | DOI Listing |
Clin Cancer Res
January 2025
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Purpose: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC).
View Article and Find Full Text PDFCancer Res Commun
January 2025
Indiana University School of Medicine, Bloomington, IN, United States.
Ovarian cancer is a deadly gynecological disease with frequent recurrence. Current treatments for patients include platinum-based therapy regimens with PARP inhibitors specific for HR-deficient high-grade serous ovarian cancers (HGSOCs). Despite initial effectiveness, patients inevitably develop disease progression as tumor cells acquire resistance.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, T2N 2T9, Canada.
Intratumoral heterogeneity (ITH) is spatial, phenotypic, or molecular differences within the same tumor that have important implications for accurate tumor classification and assessment of predictive biomarkers. The Canadian Ovarian Experimental Unified Resource (COEUR) has created a cohort of 437 FFPE tissue specimens from 108 tubo-ovarian high-grade serous carcinoma (HGSC) patients to quantify ITH across the anatomical sites and between primary and recurrence. We quantified the ITH of six clinically used immunohistochemical diagnostic and prognostic biomarkers (WT1, p53, p16, PR, CD8, and Ki67).
View Article and Find Full Text PDFPrz Menopauzalny
December 2024
Department of Surgical and Endoscopic Gynecology, Medical University of Lodz, Lodz, Poland.
Introduction: Ovarian cancer is a significant cause of death among females. MiRNAs, particularly the miR-196 family, can influence tumor progression by targeting specific pathways. Detecting ovarian cancer early is challenging, highlighting the need for additional biomarkers such as miRNAs to improve diagnosis and treatment strategies.
View Article and Find Full Text PDFMedicine (Baltimore)
November 2024
Department of Obstetrics & Gynecology, Chungnam National University School of Medicine, Chungnam National University Sejong Hospital, Sejong, Republic of Korea.
The use of neoadjuvant chemotherapy (NAC) as a first-line therapy for advanced high-grade serous ovarian carcinoma (HGSOC) has increased. However, several studies have reported NAC-induced platinum resistance. This study aimed to evaluate the predictive impact of clinical factors on chemotherapy response score (CRS) and to select patients who would respond well to NAC.
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