DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer

• DOI: 10.1016/j.isci.2025.111943
• Publication Date: 2025-02-01T07:36:41Z
• Authors: Caterina De Rosa; Floriana Morgillo; Luisa Amato; Francesca Iommelli; Viviana De Rosa; Virginia Tirino; Federica Papaccio; Concetta Tuccillo; Gaetano Di Guida; Domenico Michele ...; Alessandra Di Liello; Silvia Zappavigna; Michele Caraglia; Antonio Gambardella; Valerio Nardone; Kavya Ramkumar; Qi Wang; Jing Wang; Ferdinando De Vita; Davide Ciardiello; Erika Martinelli; Teresa Troiani; Stefania Napolitano; Giulia Martini; Alberto Servetto; Lauren Averett Byers; Fortunato Ciardiello; Carminia Maria De...

Small cell lung cancer (SCLC) is a highly aggressive form of with limited treatment options. Patients often respond well to initial chemo-immunotherapy but relapse quickly, necessitating new strategies enhance immune responsiveness. Recent research explores combining DNA-damaging therapies immunotherapy activate the STING pathway and improve antitumor response. The addition DNA Damage Repair (DDR) inhibitors, such as DNA-PKcs after chemotherapy has shown promise in activating innate sensors enhancing CD8+ T NK pathways SCLC models. This approach could potentially reshape tumor microenvironment sustain an response, offering maintenance strategy for treatment.