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Malignant cells can tolerate and resist drug treatments due to their biological flexibility. Specifically, slow-cycling drug-resistant cells may achieve permanent resistance to the treatment or restore sensitivity upon cessation of therapy. Enhancing cancer treatment methodologies necessitates a deeper understanding of the adaptability of tumor cells. Drug resistance and cellular heterogeneity are closely associated with cancer cell adaptability. Alterations in cellular signaling, interactions with the tumor microenvironment, and genetic and epigenetic alterations are all implicated. Analyzing these pathways will enhance our understanding of how cancer cells evolve and evade treatment. Two effective strategies to address cancer cell adaptability are to target specific biological pathways and to employ combination therapies. The progression of cancer therapy methodologies relies on comprehending and exploring the concept of cancer cell adaptability. Understanding tumor heterogeneity and drug resistance necessitates identifying the cellular, molecular, and genetic processes that govern cancer cell plasticity. This understanding enables the development of more personalized and effective cancer therapies, leading to improved treatment outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical trial number<\/jats:title>\n            <jats:p>Not applicable.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s41065-025-00564-8","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T10:32:00Z","timestamp":1758882720000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Cancer cell plasticity and therapeutic resistance: mechanisms, crosstalk, and translational perspectives"],"prefix":"10.1186","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-3159","authenticated-orcid":false,"given":"Saeid","family":"Ghorbian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"564_CR1","doi-asserted-by":"publisher","first-page":"891652","DOI":"10.3389\/fonc.2022.891652","volume":"12","author":"TB Emran","year":"2022","unstructured":"Emran TB, Shahriar A, Mahmud AR, Rahman T, Abir MH, Siddiquee MF, Ahmed H, Rahman N, Nainu F, Wahyudin E, Mitra S. 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