Genomics of uterine malignancies and the potential of precision medicine
Journal Title
Therapeutic Advances in Medical Oncology
Publication Type
Nov 24
Abstract
Uterine malignancies represent a broad and heterogeneous group of neoplasms, which collectively account for the majority of gynaecological malignancies in developed countries. For a significant proportion of these, mortality rates and clinical outcomes are of major concern, owing to complex molecular profiles and aggressive phenotypes that are largely refractory to conventional therapeutic approaches. Recent advancements in precision medicine and the development of targeted therapies have been transformative for several common cancer types; however, the same benefits are yet to be realised for many uterine cancers. This review comprehensively details the diverse molecular features characterising the various subtypes of uterine malignancies. Furthermore, we have examined the therapeutic approaches actively investigated to target these unique molecular features, identifying pathways and treatments that offer the greatest potential patient benefit. Among increasingly personalised strategies, particular promise is shown by HER2-targeted therapies for HER2-positive malignancies (e.g. trastuzumab deruxtecan). Additionally, targeting TP53 wild-type tumours with selinexor, as well as addressing AKT and DNA repair pathways in both uterine carcinomas and sarcomas (i.e. AKT inhibitor and poly(ADP-ribose) polymerase inhibitor combinations), represents key advancements. Furthermore, anti-angiogenic and immune checkpoint inhibitor combinations hold significant promise for future therapeutic strategies.; Investigating the potential of matching drugs to specific molecular changes in uterine cancers Uterine malignancies represent a common and complex group of cancers affecting many individuals. Unfortunately, a significant proportion of these are very aggressive and challenging to treat with standard methods. Recent progress in matching treatments based on DNA and molecular changes in individual malignancies have been transformative for several common cancer types, however the same benefits are yet to be shown for many uterine malignancies. In this review, we explore new treatments that are currently being studied to specifically target these genetic and molecular features, highlighting the personalised approaches that show the most promise for patients.; eng
Publisher
Sage
Keywords
clinical trials; molecular testing; molecular therapeutics; precision oncology; targeted therapy; uterine cancer
Research Division(s)
Cancer Biology and Stem Cells
PubMed ID
41306899
Open Access at Publisher's Site
https://doi.org/10.1177/17588359251387395
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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