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FABP5 Inhibition against PTEN-Mutant Therapy Resistant Prostate Cancer.

Manojit M Swamynathan1,2, Grinu Mathew1,3, Andrei Aziz1

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

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|January 11, 2024
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Summary
This summary is machine-generated.

A new mouse model, RapidCaP, mimics lethal prostate cancer (PC). Targeting Fatty Acid Binding Protein 5 (FABP5) with SBFI-103 shows promise for treating advanced PC resistant to standard therapies.

Keywords:
FABP5PTEN tumor suppressorRapidCaPSBFI-103androgen deprivation therapy (ADT)apalutamide resistancecastration-resistant prostate cancer (CRPC)enzalutamide resistancefatty acid binding proteins (FABPs)genetically engineered mouse (GEM) models of human cancerlipid signalingmetastatic castration-resistant prostate cancer (mCRPC)prostate cancer (PC)taxane resistance

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer (PC) resistance to taxane and androgen deprivation therapy (ADT) leads to most PC deaths.
  • PTEN and p53 loss are common drivers in lethal PC.
  • Fatty Acid Binding Proteins (FABPs) are implicated in various cancers.

Purpose of the Study:

  • To develop a preclinical model for lethal prostate cancer.
  • To identify therapeutic targets in PTEN-deficient PC.
  • To evaluate FABP5 as a therapeutic target in advanced prostate cancer.

Main Methods:

  • Development of the RapidCaP (RCaP) autochthonous genetically engineered mouse model.
  • Analysis of primary RCaP cells and large-scale patient datasets.
  • In vitro and in vivo evaluation of the FABP5 inhibitor SBFI-103.

Main Results:

  • The RapidCaP model recapitulates lethal PC with resistance to ADT and taxanes.
  • FABP5 was identified as a key target in PTEN-deficient PC.
  • SBFI-103 demonstrated efficacy in eliminating RCaP tumor cells in vivo with good tolerability.

Conclusions:

  • The RapidCaP model provides a platform for studying incurable PC.
  • FABP5 is a crucial driver in PTEN-deficient prostate cancer.
  • Targeting FABP5 with SBFI-103 offers a potential therapeutic strategy for advanced prostate cancer.