DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer
Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer with limited treatment options. Patients often respond well to initial chemo-immunotherapy but relapse quickly, necessitating new strategies to enhance immune responsiveness. Recent research explores combining DNA-damaging therapies with immunotherapy to activate the STING pathway and improve the antitumor immune response. The addition of DNA Damage Repair (DDR) inhibitors, such as DNA-PKcs inhibitors, after chemotherapy has shown promise in activating innate immune sensors and enhancing CD8<sup>+</sup> T cell and NK cell pathways in SCLC models. This approach could potentially reshape the tumor microenvironment and sustain an antitumor immune response, offering a maintenance strategy for SCLC treatment.
Authors
- Stefania Napolitano (ORCID: https://orcid.org/0000-0003-3504-8349)
- Ferdinando De Vita (ORCID: https://orcid.org/0000-0002-7654-7470)
- Francesca Iommelli (ORCID: https://orcid.org/0000-0002-5132-3593)
- Alessandra Di Liello
- Floriana Morgillo (ORCID: https://orcid.org/0000-0002-9167-323X)
- Concetta Tuccillo (ORCID: https://orcid.org/0000-0001-8713-2169)
- Virginia Tirino (ORCID: https://orcid.org/0000-0003-2731-5718)
- Kavya Ramkumar (ORCID: https://orcid.org/0000-0002-5864-2204)
- Antonio Gambardella (ORCID: https://orcid.org/0000-0002-4125-0618)
- Fortunato Ciardiello (ORCID: https://orcid.org/0000-0002-4661-5540)
- Davide Ciardiello (ORCID: https://orcid.org/0000-0003-1826-0305)
- Teresa Troiani
- Silvia Zappavigna
- Carminia M. Della Corte (ORCID: https://orcid.org/0000-0002-3396-8099)
- Federica Papaccio (ORCID: https://orcid.org/0000-0002-0302-8696)
- Alberto Servetto (ORCID: https://orcid.org/0000-0003-3624-224X)
- Viviana De Rosa (ORCID: https://orcid.org/0000-0002-0430-5608)
- Lauren A. Byers (ORCID: https://orcid.org/0000-0002-0780-2677)
- Michele Caraglia (ORCID: https://orcid.org/0000-0003-2408-6091)
- Erika Martinelli (ORCID: https://orcid.org/0000-0002-7108-0971)
- Gaetano Di Guida
- Giulia Martini (ORCID: https://orcid.org/0000-0003-4093-2681)
- Valerio Nardone (ORCID: https://orcid.org/0000-0002-7347-0965)
- Domenico Michele D'Angiolella
- Jing Wang (ORCID: https://orcid.org/0000-0002-0398-862X)
- Qi Wang (ORCID: https://orcid.org/0000-0003-2427-7234)
- Caterina De Rosa (ORCID: https://orcid.org/0000-0001-6540-0708)
- Luisa Amato (ORCID: https://orcid.org/0009-0005-6511-8071)
Institutions
- University of Salerno (IT)
- The University of Texas MD Anderson Cancer Center (US)
- University of Campania "Luigi Vanvitelli" (IT)
- Biogem (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Institute of Biostructure and Bioimaging (IT)
- National Research Council (IT)
- European Institute of Oncology (IT)
- University of Naples Federico II (IT)
Publication Details
- Journal
- iScience
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1016/j.isci.2025.111943
- Citations
- 5
- Primary Topic
- Lung Cancer Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 5.23
Funders
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health
- National Cancer Institute