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While TKIs have demonstrated effectiveness in the treatment of multiple malignancies, including chronic myelogenous leukemia, gastrointestinal tumors, non-small cell lung cancers, and HER2-overexpressing breast cancers, as is almost always the case with anti-neoplastic agents, the development of resistance often imposes a limit on drug efficacy. One common survival response utilized by tumor cells to ensure their survival in response to different stressors, including anti-neoplastic drugs, is that of autophagy. The autophagic machinery in response to TKIs in multiple tumor models has largely been shown to be cytoprotective in nature, although there are a number of cases where autophagy has demonstrated a cytotoxic function. In this review, we provide an overview of the literature examining the role that autophagy plays in response to TKIs in different preclinical tumor model systems in an effort to determine whether autophagy suppression or modulation could be an effective adjuvant strategy to increase efficiency and\/or overcome resistance to TKIs.<\/jats:p>","DOI":"10.3390\/cancers16172989","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T03:57:06Z","timestamp":1724817426000},"page":"2989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0353-1643","authenticated-orcid":false,"given":"Ahmed M.","family":"Elshazly","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 401 College St., Richmond, VA 23298, USA"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2451-8037","authenticated-orcid":false,"given":"Jingwen","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nebras","family":"Melhem","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa 13133, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alsayed","family":"Abdulnaby","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya A.","family":"Elzahed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-1107","authenticated-orcid":false,"given":"Tareq","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Public Health, Faculty of Medicine, Hashemite University, Zarqa 13133, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0437-4934","authenticated-orcid":false,"given":"David A.","family":"Gewirtz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, 401 College St., Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-397918-6.00001-X","article-title":"Catalytic mechanisms and regulation of protein kinases","volume":"548","author":"Wang","year":"2014","journal-title":"Methods Enzym."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12943-018-0801-5","article-title":"Advances in studies of tyrosine kinase inhibitors and their acquired resistance","volume":"17","author":"Jiao","year":"2018","journal-title":"Mol. 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