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Abstract Prostate cancer is estimated to contribute to over 34, 000 deaths in men residing in the United States, with the majority fatality due to metastatic disease. CDC7 is a kinase that regulates DNA replication and is an emerging cancer biomarker for poor prognosis in carcinomas such as Wilms tumor and hepatocellular carcinomas. In this study, we demonstrated that high level of CDC7 is associated with metastatic prostate cancer when compared to benign prostate tissues or localized prostate cancer. Furthermore, we found that CDC7 expression is highest in prostate cancer patient-derived xenografts (PDX) models of adenocarcinomas with neuroendocrine features. In vitro, we showed that inhibition of CDC7 with TAK-931, a CDC7 specific inhibitor, reduced the ability of aggressive prostate cancer cells to proliferate, migrate, and invade. Similarly, knock-down of CDC7 in prostate cancer cell lines inhibited cell growth in a colony formation assay. TAK-931 treated prostate cancer cell lines also showed an abnormal cell cycle profile, indicating that inhibiting CDC7 in aggressive prostate cancer could contribute to replication stress and promote apoptosis. Overall, this study demonstrates that CDC7 is a targetable protein that regulates advanced and aggressive prostate cancer growth. Citation Format: Alifiani Bonita Hartono, Sidharth Paparaju, Chung Lee, Shiqin Liu, Busola R. Alabi, En-Chi Hsu, James D. Brooks, Eva Corey, Tanya Stoyanova. CDC7 is a targetable regulator of advanced prostate cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5968.
Hartono et al. (Fri,) studied this question.