Abstract
In 2025, gynecological cancers are projected to account for approximately 10% of cancer-related deaths in women. High-grade serous ovarian carcinoma (HGSC) and serous endometrial carcinoma (SEC) are the most lethal gynecological cancer subtypes. Both malignancies commonly have TP53 mutations, alterations of the RB1 pathway, and numerous secondary mutations. Both carcinoma types consist of poorly differentiated and highly heterogeneous cell populations at the time of detection. Latent development and rapid progression of HGSC and SEC impede the identification of definitive cells of origin and genetic drivers. Here, we review our current knowledge about cancer-prone cell states and genetic drivers. We also discuss how emerging transcriptomic and genetic tools applied to contemporary model systems may facilitate the identification of novel targets for timely detection and therapeutic intervention.