Abstract 6436: Tumor-educated platelets for therapy stratification of metastasized castration resistant prostate cancer (CRPC)

Abstract

Abstract One in ten men diagnosed with prostate cancer will have metastases. At some point the metastases becomes castration therapy resistant, contributing leading to the high mortality of prostate cancer. Novel androgen directed treatments, like abiraterone and enzalutamide, have made substantial difference to therapy response, yet only within subgroups of CRPC patients. Correct therapy stratification may prolong the life of the patients, possibly turning a deadly disease into a more chronic disease. For this to happen we need predictive biomarkers that can be used to longitudinally follow the disease in order to identify vulnerabilities and to monitor acquired resistance, e.g. we need to develop personalized liquid biopsy platforms. Using the platelet enriched fraction of a blood sample we here show that we can use the platelets ability to sequester material during circulation to provide information derived from the tumor, a.k.a. tumor-educated platelets. This information could be used as a companion diagnostic to identify patients that will respond to therapy, and to longitudinally monitor tumor progression. In this study, a previously published three gene profile, plt3G profile, was validated in a larger cohort (n=97) and showed that combined analysis of the three genes transcripts (KLK3, FOLH1, NPY) could be used to identify long-term responders regarding progression-free survival after enzalutamide (n=47; PFS; LR p<0,001, HR 0,32, p<0,001) or abiraterone (n=50; PFS; LR p=0.007, HR 0.45, p=0,009) -treatment. Furthermore, progression and resistance development could be accurately longitudinal followed. The plt3G profile showed a significant overlap with circulating tumor DNA (ctDNA) biomarkers, but in addition also provided predictive information around treatment response. Tumor-educated platelets provide therapy-predictive biomarkers as well as biomarkers for longitudinal monitoring of disease progression and resistance development, which ultimately could provide information for therapy switching. Their easy accessibility makes tumor-educated platelets an attractive biosource to be used alone or in combination others, to enable a fluid biomarker platform with the aim to turn a lethal cancer disease into a more chronic disease. Citation Format: Jonas A. Nilsson, Marie Lundholm, Lee-Ann Tjon-Kon-Fat, Linda Köhn, Camilla Thellenberg-Karlsson, Andreas Josefsson, Pernilla Wikström. Tumor-educated platelets for therapy stratification of metastasized castration resistant prostate cancer (CRPC) [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(6_Suppl):Abstract nr 6436.