Metastatic castration – resistant prostate cancer resistant to androgen receptor signaling inhibitors – APCCC

APCCC posted on X:

“Genomic and epigenomic analysis of plasma cell-free DNA identifies stemness features associated with worse survival in lethal prostate cancer Out on CCR AACR.

Study investigates metastatic castration-resistant Prostate Cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSIs), a highly lethal form of cancer.

Using targeted and genome-wide cell-free DNA sequencing from 126 and 43 mCRPC patients, respectively, researchers found that AR/enhancer alterations in cell-free DNA prior to ARSI treatment correlated with significantly worse PFS and Overall survival.

Further analysis of the plasma methylome revealed increased promoter-level hypomethylation in patients with these alterations. Additionally, transcription factor analysis suggested that cancer lethality is driven by increased stemness. This stem-like signature was validated in a separate cohort, establishing AR/enhancer alterations as a prognostic biomarker for lethal mCRPC.

Genomic and epigenomic analysis of plasma cell-free DNA identifies stemness features associated with worse survival in lethal prostate cancer

Authors: Pradeep S. Chauhan, Irfan Alahi, Savar Sinha, Elisa M. Ledet, Ryan Mueller, Jessica Linford, Alexander L. Shiang, Jace Webster, Lilli Greiner, Breanna Yang, Gabris Ni, Ha X. Dang, Debanjan Saha, Ramandeep K. Babbra, Wenjia Feng, Peter K. Harris, Faridi Qaium, Dzifa Y. Duose, Alexander Sanchez-Espitia, Alexander D. Sherry, Ellen B. Jaeger, Patrick J. Miller, Sydney A. Caputo, Jacob J. Orme, Fabrice Lucien, Sean S. Park, Chad Tang, Russell K. Pachynski, Oliver Sartor, Christopher A. Maher, Aadel A. Chaudhuri.”

Source: Advanced Prostate Cancer Consensus Conference/X