SLFN11 Expression in Advanced Prostate Cancer and Response to Platinum-based Chemotherapy.

Molecular Cancer Therapeutics
Vincenza ConteducaHimisha Beltran

Abstract

Expression of the DNA/RNA helicase schlafen family member 11 (SLFN11) has been identified as a sensitizer of tumor cells to DNA-damaging agents including platinum chemotherapy. We assessed the impact of SLFN11 expression on response to platinum chemotherapy and outcomes in patients with metastatic castration-resistant prostate cancer (CRPC). Tumor expression of SLFN11 was assessed in 41 patients with CRPC treated with platinum chemotherapy by RNA sequencing (RNA-seq) of metastatic biopsy tissue (n = 27) and/or immunofluorescence in circulating tumor cells (CTC; n = 20). Cox regression and Kaplan-Meier methods were used to evaluate the association of SLFN11 expression with radiographic progression-free survival (rPFS) and overall survival (OS). Multivariate analysis included tumor histology (i.e., adenocarcinoma or neuroendocrine) and the presence or absence of DNA repair aberrations. Patient-derived organoids with SLFN11 expression and after knockout by CRISPR-Cas9 were treated with platinum and assessed for changes in dose response. Patients were treated with platinum combination (N = 38) or platinum monotherapy (N = 3). Median lines of prior therapy for CRPC was two. Median OS was 8.7 months. Overexpression of SLFN11 in metas...Continue Reading

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Citations

Sep 24, 2020·International Journal of Cancer. Journal International Du Cancer·Peter H J SlootbeekNiven Mehra
Feb 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ukhyun JoYves Pommier
Dec 20, 2020·British Journal of Cancer·Claudia WinklerElisabetta Leo
Feb 12, 2021·Prostate Cancer and Prostatic Diseases·Jacob E BerchuckAna Aparicio
Dec 18, 2020·British Journal of Cancer·Niamh ColemanTimothy A Yap
Feb 21, 2021·European Urology·Shilpa Gupta, Hannelore V Heemers
Apr 1, 2021·British Journal of Cancer·Tsuyoshi TakashimaWataru Yasui
Jul 24, 2021·British Journal of Cancer·Bingnan ZhangLauren Averett Byers

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