TAM family kinases as therapeutic targets at the interface of cancer and immunity.

Autor: DeRyckere D; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.; Department of Paediatrics, Emory University School of Medicine, Atlanta, GA, USA., Huelse JM; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.; Department of Paediatrics, Emory University School of Medicine, Atlanta, GA, USA., Earp HS; Department of Medicine, UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.; Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Graham DK; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA. douglas.graham@choa.org.; Department of Paediatrics, Emory University School of Medicine, Atlanta, GA, USA. douglas.graham@choa.org.
Jazyk: angličtina
Zdroj: Nature reviews. Clinical oncology [Nat Rev Clin Oncol] 2023 Nov; Vol. 20 (11), pp. 755-779. Date of Electronic Publication: 2023 Sep 04.
DOI: 10.1038/s41571-023-00813-7
Abstrakt: Novel treatment approaches are needed to overcome innate and acquired mechanisms of resistance to current anticancer therapies in cancer cells and the tumour immune microenvironment. The TAM (TYRO3, AXL and MERTK) family receptor tyrosine kinases (RTKs) are potential therapeutic targets in a wide range of cancers. In cancer cells, TAM RTKs activate signalling pathways that promote cell survival, metastasis and resistance to a variety of chemotherapeutic agents and targeted therapies. TAM RTKs also function in innate immune cells, contributing to various mechanisms that suppress antitumour immunity and promote resistance to immune-checkpoint inhibitors. Therefore, TAM antagonists provide an unprecedented opportunity for both direct and immune-mediated therapeutic activity provided by inhibition of a single target, and are likely to be particularly effective when used in combination with other cancer therapies. To exploit this potential, a variety of agents have been designed to selectively target TAM RTKs, many of which have now entered clinical testing. This Review provides an essential guide to the TAM RTKs for clinicians, including an overview of the rationale for therapeutic targeting of TAM RTKs in cancer cells and the tumour immune microenvironment, a description of the current preclinical and clinical experience with TAM inhibitors, and a perspective on strategies for continued development of TAM-targeted agents for oncology applications.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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