Abstract Breast and prostate cancer are aggressive hormone-dependent diseases that affect thousands of people every year. Despite advances in early detection and the understanding of the molecular bases of both cancers' biology, resistance to therapy frequently occurs. Thus, the identification of novel therapeutic targets and pathways that contribute to breast and prostate cancer lethality is necessary for improving clinical outcomes. Here, we analyzed the gene expression of known inhibitors of the protein phosphatase 2A (PP2A) in both cancer patient samples. Our analysis disclosed a general over-expression of all PP2A negative regulators. Additionally, SET, CIP2A, ANP32E and TIPRL genes are frequently co-expressed, and their expression positively correlates with the ones of the main cyclins and CDKs, suggesting the existence of a feed-forward loop that might contribute to the cancer progression via PP2A inactivation. Overall, our study indicates the existence of a strategic and targetable axis between PP2A inhibitors (SET, CIP2A, ANP32E and TIPRL) and cell cycle regulators (Cyclin A, Cyclin E, Cyclin B and CDK1) and provides a valuable rationale for using a personalized combinational therapy approach to improve breast and prostate cancer patient survival. Keywords: Breast cancer, Prostate Cancer, PP2A, cell cycle Citation Format: Ylenia Cendon-Florez, Raffaella Pippa, Silvia Boffo, Maria D. Odero, Antonio Giordano. Data mining analysis of the PP2A-cell cycle axis in breast and prostate cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 107.