Abstract 6823: Dynamics of KMT2D modulation of the PI3K-Akt pathway and the impact on metastasis in prostate cancer

Abstract Despite advances in the treatment of prostate cancers, such as androgen receptor (AR) inhibitors and androgen depreivation therapies (ADT), relapse often occurs, which leads to drug resistant forms of prostate cancer. Understanding the mechanism behind resistance thus becomes important for developing effective treatments. Epigenetic regulators such as KMT2D, a histone 3 lysine 4 methlytransferase, have been implicated in modulating signature pathways associated with cell progression and survival. The PI3K-AKT-mTOR pathway has been studied by many in the field on its role in cancer progression and treatment resistance. However, not as much is known about it being epigenetically regulated. Our preliminary studies demonstrate an association of KMT2D expression/activity and the PI3K-AKT signaling pathway. Interestingly, enrichment analysis in KMT2D knockout treatment-resistant prostate cancer models and their respective controls, demonstrated enriched signatures associated with tumor metastasis and cell adhesion downregulated. While these studies are still preliminary, our results provides an insight to the role of KMT2D in a context dependent mannar, where in an already acquired treatment-resistant state, KMT2D may be promoting a tumor-suppressor-like program and help improve the existing treatment regimen. Ongoing studies will validate our preliminary findings and provide a better understanding of the correlation between KMT2D and these genes along with the PI3K-Akt-mTOR signaling pathway.. Citation Format: Abbas Jawadwala, Surrendra Gulla, Remi Adelaiye-Ogala. Dynamics of KMT2D modulation of the PI3K-Akt pathway and the impact on metastasis in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6823.