Abstract 2364: The role of β1 and β5 integrins as biomarkers in anti-motility therapy treatment response

Abstract Introduction. Metastasis is the major cause of mortality in patients with solid tumors. Our group has identified precision therapeutic inhibitors of cell motility and shown their ability to prevent metastasis. In striving to move novel first-in-class therapy into humans, it is important to identify biomarkers of therapeutic efficacy. As β1 and β5 integrins mediate prostate cancer cell migration, they are strong biomarker candidates. While our novel anti-motility agent, KBU2046, inhibits cell motility, its effects on β1 and β5 integrin expression and dynamics are not fully understood. We, therefore, investigated the impact of KBU2046 on β1 and β5 integrin patterns in cells and their potential as predictive biomarkers of therapeutic response. Experimental procedures. Initial screening studies consisted of orthogonal protein expression measures, including mass spectrometry and Western blot-based analytics, in the context of time- and concentration-based treatment anti-motility therapeutics. This was then followed by immunofluorescence (IF) analysis by confocal microscopy of a panel of human prostate primary and metastatic cells, examining patterns of expression under conditions of static as well as synchronized cell attachment. Results. Evaluation of the proteome through bioinformatic analytics identified changes in cell adhesion proteins as high-potential biomarkers. From this, we specifically investigated the dynamics of β1 and β5 integrins in response to antimotility treatment with KBU2046. In this manner, treatment induced significant alterations in cell morphology. This was associated with a dynamic, time-dependent redistribution of β1 and β5 integrins. The pattern of this change demonstrates disruption in normal integrin trafficking and supports a basis for disruption of normal integrin function. These findings provide orthogonal support for the established role of KBU2046 in inhibiting cell motility and identify β1 and β5 integrin expression patterns as high-potential biomarkers of therapeutic efficacy for anti-motility agents. Conclusions. Our investigation reveals that treatment with KBU2046 induces significant changes in the dynamics of β1 and β5 integrins in prostate cancer cells, disrupting their normal function and trafficking. Using IF and protein expression analyses, we identified β1 and β5 integrins as potential biomarkers indicative of therapeutic efficacy in response to anti-motility treatment. These findings underscore the significance of β1 and β5 integrin expression patterns as key indicators for assessing the effectiveness of future anti-motility strategies. Further investigation of these biomarkers in clinical settings could offer valuable insights to inform therapeutic decisions in the treatment of prostate cancer. Citation Format: Weining Chen, Nicholas Woods, Henry Chun Hin Law, Fangfang Qiao, Raymond C. Bergan. The role of β1 and β5 integrins as biomarkers in anti-motility therapy treatment response [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 2364.