Abstract 6349: Degradation of Aurora Kinase A, Alters Immune Checkpoint Expressions in Prostate Cancer

Abstract Pre-metastatic niche of tumor microenvironment supports tumor progression and regulates cancer cell survival. Aurora kinase A is a key molecule implicated in establishing this niche by promoting tumor cell migration, invasion, and survival within the secondary organ, thus contributing to metastasis. The Cancer Genome Atlas program data suggested increased expression of Aurora Kinase A (AURKA), Ninein (NIN) and Aurora Kinase A Ninein Interacting Protein (AUNIP) in prostate cancer as compared to normal prostate tissue. We are exploring how these interactions might influence immune cell infiltration, both in immune-responsive and immune-suppressive cells. Regulation of immune checkpoint proteins like PD-L1 and LAG3 is crucial for immune evasion by cancer cells. This study investigates the effects of a novel AURKA degrader compound, SP-02-067, on the downstream signaling cascade that regulates immune checkpoints PD-L1 and LAG3. We analyzed expression data of 702 prostate cancer patients using the Tumor Immune Microenvironment Estimation Resource and involved various immune responsive (CD8+; dendritic cells; natural killer) and immune suppressive (T-reg; myeloid derived suppressor cells; neutrophils) cells. Gene expression analysis showed significant correlation between NIN and PD-L1 (R = 0.12, p = 0.01), NIN and LAG3 (R = -0.22, p < 0.001). Combined immune responsive and combined immune suppressive cells were significantly associated with AURKA (R = 0.03, p = 0.24), NIN (R = 0.1, p = 0.1) and AUNIP (R = 0.13, p = 0.21) expression. Next, we treated prostate cancer C4-2 cells with varying concentrations of the novel SP-02-067 compound in a time-dependent manner, which led to degradation of AURKA and altered expressions of PD-L1 and LAG-3. Using an siRNA gene silencing approach for AURKA and AUNIP in C4-2 cells showed increased expression of PD-L1 and decreased LAG3 expression. The data suggests that increased expression of PD-L1 may be associated with an increase in tumor infiltrating cells, which could improve the efficacy of subsequent immunotherapy. Spearman correlation showed a positive correlation with infiltrating immune-responsive CD8+ T cells, dendritic cells, and NK cells. Similarly, immune suppressive regulatory T-cells and neutrophils were positively correlated with LAG3. Based on these findings, we suggest that SP-02-067, a novel degrader of AURKA, could be developed as a promising agent for prostate cancer and inspire innovative approaches to overcome drug resistance in prostate tumor-targeted therapy. Citation Format: Sanjeev Shukla, Arjun Venkatesh, Jean-Pierre Kanumuambidi, Reynier D. Rodriguez Rosales, Mohammed Al-Toubat, Shelby Sparks, Adriana Yamaguchi, Steven Fletcher, K.C. Balaji. Degradation of Aurora Kinase A, Alters Immune Checkpoint Expressions 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 6349.