In the relentless battle against non-small cell lung cancer (NSCLC) driven by epidermal growth factor receptor (EGFR) mutations, the development of resistance has long been a formidable obstacle. Historically, first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) like gefitinib, erlotinib, afatinib, and dacomitinib have faced a significant hurdle: the emergence of the T790M point mutation in approximately 50% of patients, rendering the tumor resistant to these therapies. This resistance stems from a sobering reality – before treatment, a small subset of cancer cells already harbor the T790M mutation, conferring no selective advantage initially. However, once treatment commences, these rare mutated cells proliferate selectively, eventually dominating the tumor population and diminishing the effectiveness of first- and second-generation TKIs. Full blog - https://www.oncotarget.org/2024/06/06/dr-blagosklonnys-strategy-from-osimertinib-to-preemptive-combinations/ Paper DOI - https://doi.org/10.18632/oncotarget.28569 Correspondence to - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com Video short - https://www.youtube.com/watch?v=UO5BGLIggTE Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28569 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, lung cancer, NSCLC, EGFR, resistance, afatinib, gefitinib, capmatinib About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957