Targeting TCTP as a new therapeutic strategy in castration-resistant prostate cancer

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Heat shock protein 27 (Hsp27) is overexpressed in castration-resistant prostate cancer (CRPC).
• Understanding Hsp27's mechanisms and identifying CRPC-specific therapeutic targets are crucial.

Purpose of the Study:

• To identify Hsp27 client proteins involved in CRPC cytoprotection.
• To investigate the role of translationally controlled tumor protein (TCTP) in CRPC.

Main Methods:

• Screening for Hsp27 client proteins.
• Assessing TCTP expression in normal prostate, treatment-naive, and CRPC tissues.
• Developing and utilizing a TCTP antisense oligonucleotide (ASO).
• Evaluating the effect of TCTP knockdown on P53 expression and function.

Main Results:

• Translationally controlled tumor protein (TCTP) was identified as a novel Hsp27 client protein involved in cytoprotection.
• TCTP expression is significantly elevated in CRPC compared to normal and treatment-naive prostate cancer.
• CRPC progression correlates with TCTP overexpression and loss of P53; TCTP knockdown restored P53.
• Developed and patented a TCTP-targeting ASO.

Conclusions:

• TCTP is a key mediator of Hsp27-driven cytoprotection in CRPC.
• TCTP overexpression and P53 loss are linked in CRPC progression.
• ASO-mediated TCTP knockdown presents a potential therapeutic strategy for CRPC, possibly enhancing castration and docetaxel therapies with low toxicity.