Cell cycle checkpoint proficiency of endometrial cancer cells [bulk RNA-Seq]

Endometrial cancers (EC) are the most common gynecologic malignancy in the US. Most ECs harbor limited targetable somatic alterations, and are often grouped by histology (endometrioid, serous, or clear cell), mismatch repair, or TP53 status, none of which perfectly predict therapeutic response. A better mechanistic understanding of the key functional defects in ECs and more therapies with which to engage those targets in advanced stage EC are needed. Here we utilize functional, transcriptomic and genomic assays on a panel of EC cell lines and patient-derived organoids across EC histologic and genomic subtypes to characterize the TP53 and RB1 cell cycle regulatory proficiency and therapeutic vulnerabilities in this disease. We were surprised to find that TP53 genomic and functional status has little predictive capacity for EC therapeutic response. Rather, RB regulatory status correlated better with response to G1/S targeted therapies.