[225Ac]Ac-PSMA-617 mutational landscape in circulating tumor DNA (ctDNA): early clinical outcome prediction in metastatic castration-resistant prostate cancer

First clinical experiences employing PSMA (prostate-specific membrane antigen) with alpha-particle-emitting radionuclide actinium-225 (225Ac) exhibited astonishing responses in heavily pre-treated metastatic castration- and chemo-resistant prostate cancer (PCa) patients. Thus, our most recent efforts have been directed toward the investigation of functional predispositions of PCa-related radiation resistance and sensitivity to PSMA-directed targeted alpha therapy (TαT) with [225Ac]Ac-PSMA-617. Preclinical and clinical studies reported that particular DNA-damage repair (DDR)-associated gene mutations can either increase or decrease the radiosensitivity of PCa. Therefore, non-invasive liquid biopsies, detecting early clinical outcome, represent an unmet clinical need. Deep whole-genome circulating tumor DNA (ctDNA) and its matching germline DNA (gDNA) sequencing will address the molecular alpha emitters-based radiation resistance mechanisms.

AMGHAR Mariam;  RAUSCH Tobias;  HIELSCHER Thomas;  OZGUR Hilal;  ROSCHER Mareike;  BAUDER-WÜST Ulrike;  SCHICK Matthias;  REMDE Yvonne;  BAKOS Gabor;  SCHÄFER Martin;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  BENES Vladimir;  KRATOCHWIL Clemens;  BENESOVA-SCHÄFER Martina; 

2023-10-11

SPRINGER

JRC134430

1619-7070 (online),   

https://link.springer.com/article/10.1007/s00259-023-06333-x,    https://publications.jrc.ec.europa.eu/repository/handle/JRC134430,   

10.1007/s00259-023-06333-x (online),