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),
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