{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:29:51Z","timestamp":1790357391876,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-small cell lung cancer (NSCLC) remains a disease with a poor prognosis despite the advances in therapies. NSCLC with actionable oncogenic alterations represent a subgroup of diseases for which tyrosine kinase inhibitors (TKIs) have shown relevant and robust impact on prognosis, both in early and advanced stages. While the introduction of powerful TKIs increases the ratio of potentially curable patients, the disease does develop resistance over time through either secondary mutations or bypass activating tracks. Therefore, new treatment strategies are being developed to either overcome this inevitable resistance or to prevent it, and proteolysis targeting chimera agents (PROTACs) are among them. They consist of two linked molecules that bind to a target protein and an E3 ubiquitin ligase that causes ubiquitination and degradation of proteins of interest. In this paper, we review the rationale for PROTAC therapy and the current development of PROTACs for oncogene-addicted lung cancer. Moreover, we critically analyze the strengths and limitations of this promising technique that may help pave the way for future perspectives.<\/jats:p>","DOI":"10.3390\/ijms252011214","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T05:03:49Z","timestamp":1729227829000},"page":"11214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Proteolysis Targeting Chimera Agents (PROTACs): New Hope for Overcoming the Resistance Mechanisms in Oncogene-Addicted Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3227-8280","authenticated-orcid":false,"given":"Nicoletta","family":"Cordani","sequence":"first","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Nova","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4568-5739","authenticated-orcid":false,"given":"Luca","family":"Sala","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Ida","family":"Abbate","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Colonese","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-7369","authenticated-orcid":false,"given":"Diego Luigi","family":"Cortinovis","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"},{"name":"Medical Oncology Unit, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Canova","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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