Unraveling resistance mechanisms to the novel nucleoside analog RX-3117 in lung cancer: insights into DNA repair, cell cycle dysregulation and targeting PKMYT1 for improved therapy
By integrating CRISPR-Cas9 with functional assays and transcriptomics, our study established a framework for decoding resistance mechanisms and highlights potential therapeutic strategies to enhance RX-3117 efficacy in NSCLC. We demonstrated for the first time that aberrant DNA repair and cell cycle dysregulation led resistance, identifying PKMYT1 as a promising target.
Authors
- Sabrina Strano (ORCID: https://orcid.org/0000-0002-6341-4230)
- Bing Wang
- Richard J. Honeywell (ORCID: https://orcid.org/0000-0001-9415-5959)
- Dzjemma Sarkisjan
- Giulia Mantini
- Btissame El Hassouni
- Godefridus J. Peters (ORCID: https://orcid.org/0000-0002-5447-2877)
- Elisa Giovannetti (ORCID: https://orcid.org/0000-0002-7565-7504)
- Mahrou Vahabi
- Valentina Donati (ORCID: https://orcid.org/0000-0003-0181-915X)
- Giovanni Blandino (ORCID: https://orcid.org/0000-0002-6970-2241)
- Dongmei Deng (ORCID: https://orcid.org/0000-0003-3706-1678)
- Giulia Lencioni (ORCID: https://orcid.org/0009-0008-6521-337X)
- Geng Xu (ORCID: https://orcid.org/0000-0002-4597-8729)
Institutions
- Fondazione Pisa (IT)
- Academic Center for Dentistry Amsterdam (NL)
- Amsterdam Neuroscience (NL)
- Amsterdam University Medical Centers (NL)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Azienda Ospedaliera Universitaria Pisana (IT)
- Gdańsk Medical University (PL)
- Vrije Universiteit Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Publication Details
- Journal
- Journal of Experimental & Clinical Cancer Research
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1186/s13046-025-03470-z
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Amsterdam University Medical Centers
- KWF Kankerbestrijding
- Mashhad University of Medical Sciences
- Nanjing Medical University