Developing Novel AR Mutant Prostate Cancer Models

Since prostate cancer heavily depends on androgen hormones for growth, targeting the androgen receptor (AR) signaling pathway is a key therapeutic strategy for treating advanced metastatic prostate cancer. While AR antagonists like enzalutamide can significantly improve survival in prostate cancer patients, resistance often develops over time, largely driven by treatment-induced mutations within the ligand-binding domain of the AR gene.  Establishing models that harbor these AR hotspot mutations is imperative for advancing precision medicine in metastatic castration-resistant prostate cancer.

At the 2024 EORTC-NCI-AACR Symposium in Barcelona, WuXi Biology presented a poster on the development of two engineered LNCaP prostate cancer models with the AR hot spot mutations T878A/F877L and T878A/H875Y.  The authors demonstrate the potential of these models, in conjunction with a targeted protein degradation therapeutic approach, for providing insights into the mechanism of hormonal treatment resistance.

ENA 2024_Developing novel AR mutant prostate cancer models for CRPC related drug discovery

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