Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Genomic scarring score predicts the response to PARP inhibitors in non-small cell lung cancer
Δημιουργός/Συγγραφέας:	Tsilingiri, Katerina Chalari, Anna Christopoulou, Georgia [EL] Βουτσινά, Αλεξάνδρα[EN] Voutsina, Alexandra Constantoulakis, Pantelis Potaris, Κonstantinos Vamvakaris, Ioannis Hatzidaki, Dora Zachou, Georgina Vatsellas, Giannis Georgoulias, Vassilis Kotsakis, Athanasios Klinakis, Apostolos
Ημερομηνία:	2024
Γλώσσα:	Αγγλικά
ISSN:	2397-768X
DOI:	10.1038/s41698-024-00777-6
Περίληψη:	PARP inhibitors (PARPi) have shown efficacy in tumours harbouring mutations in homologous recombination repair (HRR) genes. Somatic HRR mutations have been described in patients with Non-Small Cell Lung Cancer (NSCLC), but PARP inhibitors (PARPi) are not yet a therapeutic option. Here we assessed the homologous recombination status of early-stage NSCLC and explored the therapeutic benefit of PARPi in preclinical models. The Genomic Scarring Score GSS (GSS) and HRR mutation profile of 136 patients were assessed. High GSS (h-GSS) was observed in 39 (28.7%) patients half of which carried pathogenic/likely pathogenic somatic HRR mutations. TP53 mutations were significantly enriched in h-GSS tumours (p < 0.001). Olaparib significantly delayed tumour growth in h-GSS but not l-GSS Patient-derived Xenografts (PDXs), while patients with h-GSS/TP53mut tumours respond favourably to adjuvant platinum-based chemotherapy. Our functional data clearly support the idea that the use of GSS rather than the mutational status of HRR genes could select patients for administration of PARPi.
Τίτλος πηγής δημοσίευσης:	npj Precision Oncology
Τόμος/Κεφάλαιο:	8
Τεύχος:	1
Θεματική Κατηγορία:	[EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Μοριακή Βιολογία[EN] Molecular Biology [EL] Βιοχημεία[EN] Biochemistry
Λέξεις-Κλειδιά:	PARP inhibitors (PARPi) Homologous Recombination Repair (HRR) Genomic Scarring Score (GSS) Non-Small Cell Lung Cancer (NSCLC) TP53 mutations Patient-Derived Xenografts (PDXs) platinum-based chemotherapy
EU Grant:	Tumour-LN-oC MULTIR
EU Grant identifier:	953234 101136926
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1038/s41698-024-00777-6
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο