ADAMTS9-AS2 Disrupts Docetaxel-Resistance in Castration-Resistant Prostate Cancer via Stemness Suppression and...

Area of Science:

• Oncology
• Molecular Biology
• Biomaterials

Background:

• Chemotherapy resistance in castration-resistant prostate cancer (CRPC) is a major clinical hurdle.
• Prostate tumor stem cells (PCSCs) are implicated in CRPC chemotherapy resistance, but mechanisms remain unclear.

Purpose of the Study:

• To investigate the role of ADAMTS9-AS2 in overcoming docetaxel resistance in CRPC.
• To elucidate the dual mechanisms by which ADAMTS9-AS2 reduces chemotherapy resistance.
• To explore the efficacy of novel polymeric materials targeting PCSCs to enhance chemotherapy sensitivity.

Main Methods:

• Identification of PCSC regulatory molecules using mRNAsi-based multi-center patient cohorts.
• In vitro and in vivo experiments to assess ADAMTS9-AS2's effect on docetaxel resistance.
• Development and application of polymeric materials incorporating TGF-β inhibitor, ferroptosis inducer, and miR-182-5p inhibitor.

Main Results:

• ADAMTS9-AS2 suppresses PCSC stemness via the FOXF2/TGF-β2 axis.
• ADAMTS9-AS2 promotes ferroptosis by influencing SLC7A11 localization.
• Polymeric materials targeting PCSCs significantly improved docetaxel sensitivity and inhibited tumor growth in vivo.

Conclusions:

• ADAMTS9-AS2 mitigates CRPC chemotherapy resistance through PCSC stemness suppression and ferroptosis induction.
• Targeting PCSCs with specialized polymeric materials presents a promising therapeutic strategy for overcoming CRPC chemoresistance.