Alpha-particle therapy in mCRPC: Case Studies utilizing ctDNA as a therapeutic biomarker for early clinical outcome prediction

First clinical experiences employing PSMA addressing radiopharmaceuticals/theranostics (prostate-specific membrane antigen) with the alpha-particle-emitting radionuclide actinium-225 (225Ac) showed astonishing treatment responses in metastasized castration-resistant prostate cancer (mCRPC) patients. In light of the scarcity of 225Ac alongside with eventual treatment resistance, it is crucial to identify patients who are most likely to benefit from targeted alpha-therapy (TαT) early in their treatment course. Detecting early clinical outcomes through non-invasive liquid biopsies represents an unmet clinical need in stratifying patient responsiveness. Circulating free tumor DNA (ctDNA) is a promising biomarker of disease burden and therapeutic response, since — unlike conventional markers — this metric is agnostic to cancer type. Our recent focus has been on stratifying patients based on liquid biopsies. Our case study reports the clinical courses of four distinct patient responses. By comparing clinical data and whole genome sequencing coupled with ichorCNA analysis, we aim to uncover potential mechanisms for treatment resistance and relapse encoded in the patient's cfDNA.

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

2024-12-17

SPRINGER

JRC138980

1619-7089 (online),   

https://link.springer.com/article/10.1007/s00259-024-06838-z,    https://publications.jrc.ec.europa.eu/repository/handle/JRC138980,   

10.1007/s00259-024-06838-z (online),