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This signaling plasticity provides cancer cells with a level of operational freedom, reducing treatment efficacy. Plasticity is a characteristic of cancer cells that are not only able to switch signaling pathways but also from one cellular state (differentiated cells to stem cells or vice versa) to another. It seems implausible that the inhibition of one or a few signaling pathways of heterogeneous and plastic tumors can sustain a durable effect. We propose that inhibiting molecules with pleiotropic functions such as cell surface co-receptors can be a key to preventing therapy escape instead of targeting bona fide receptors. Therefore, we ask the question whether co-receptors often considered as \u201caccessory molecules\u201d are an overlooked key to control cancer cell behavior.<\/jats:p>","DOI":"10.1007\/s10585-024-10292-4","type":"journal-article","created":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T07:01:30Z","timestamp":1716015690000},"page":"599-611","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Targeting CD44 and other pleiotropic co-receptors as a means for broad inhibition of tumor growth and metastasis"],"prefix":"10.1007","volume":"41","author":[{"given":"Lisa-Marie","family":"Mehner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonel","family":"Munoz-Sagredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen Joachim","family":"Sonnentag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven M\u00e1t\u00e9","family":"Treffert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2939-9257","authenticated-orcid":false,"given":"V\u00e9ronique","family":"Orian-Rousseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,18]]},"reference":[{"key":"10292_CR1","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41392-021-00572-w","volume":"6","author":"L Zhong","year":"2021","unstructured":"Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, Yang W, Tian C, Miao Z, Wang T, Yang S (2021) Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. 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