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January 22, 2026Cancer Research

Abstract B038: High-throughput drug screening identifies a novel synergistic therapeutic strategy co-targeting nuclear export and translation initiation in prostate cancer

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Authors

JKJessica D. KindrickKBKinjal BhadreshaXZX. ZHANG

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Overview

High-throughput drug screening identifies a new strategy to improve treatment responses in metastatic castration-resistant prostate cancer, suggesting effective combinatorial therapies.

Key Points

  • The research aims to discover effective drug combinations to combat resistance in metastatic castration-resistant prostate cancer (mCRPC).
  • Conducted high-throughput drug screening of 2,480 compounds across 8 prostate cancer cell lines.
  • Evaluated dual-drug combinations in AR-V7-expressing models using 10x10 dose matrices.
  • Utilized ExcessHSA synergy model to analyze interactions between compounds.
  • Performed in vivo testing in LNCaP-95 and LuCaP167-CR xenografts to assess tumor regression.
  • Identified significantly synergistic interactions between XPO1 and EIF4A1 inhibitors.
  • Demonstrated reduced proliferation and increased apoptosis with combined treatment in vitro.
  • Achieved remarkable tumor regression at low doses in in vivo models with no toxic effects.
  • Global proteomic profiling indicated downregulation of key oncogenic drivers and pathways.

Cite This Study

Kindrick et al. (2026) studied this question.

synapsesocial.com/papers/6971bd90642b1836717e236chttps://doi.org/10.1158/1538-7445.prostateca26-b038
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