2026-08-29T15:33:54Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/258522025-12-18T12:57:07Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Soler-Agesta, R author Moreno-Loshuertos, R author Yim, C Y author Congenie, M T author Ames, T D author Johnson, H L author Stossi, F author Mancini, M G author Mancini, M A author Ripollés-Yuba, C author Marco-Brualla, J author Junquera, C author Martínez-De-Mena, R author Enríquez, J A author Price, M R author Jimeno, J author Anel, A author 2024-10-11 PT-112 is a novel immunogenic cell death (ICD)-inducing small molecule currently under Phase 2 clinical development, including in metastatic castration-resistant prostate cancer (mCRPC), an immunologically cold and heterogeneous disease state in need of novel therapeutic approaches. PT-112 has been shown to cause ribosome biogenesis inhibition and organelle stress followed by ICD in cancer cells, culminating in anticancer immunity. In addition, clinical evidence of PT-112-driven immune effects has been observed in patient immunoprofiling. Given the unmet need for immune-based therapies in prostate cancer, along with a Phase I study (NCT#02266745) showing PT-112 activity in mCRPC patients, we investigated PT-112 effects in a panel of human prostate cancer cell lines. PT-112 demonstrated cancer cell selectivity, inhibiting cell growth and leading to cell death in prostate cancer cells without affecting the non-tumorigenic epithelial prostate cell line RWPE-1 at the concentrations tested. PT-112 also caused caspase-3 activation, as well as stress features in mitochondria including ROS generation, compromised membrane integrity, altered respiration, and morphological changes. Moreover, PT-112 induced damage-associated molecular pattern (DAMP) release, the first demonstration of ICD in human cancer cell lines, in addition to autophagy initiation across the panel. Taken together, PT-112 caused selective stress, growth inhibition and death in human prostate cancer cell lines. Our data provide additional insight into mitochondrial stress and ICD in response to PT-112. PT-112 anticancer immunogenicity could have clinical applications and is currently under investigation in a Phase 2 mCRPC study. J Transl Med. 2024 Oct 11;22(1):927. Journal of Translational Medicine 39394618 https://hdl.handle.net/20.500.12105/25852 Autophagy Immunogenic cell death Mitochondrial stress PT-112 Prostate cancer Cancer cell-selective induction of mitochondrial stress and immunogenic cell death by PT-112 in human prostate cell lines.