期刊
CURRENT MEDICINAL CHEMISTRY
卷 24, 期 16, 页码 1671-1686出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867324666170112112734
关键词
Multitargeted drugs; anticancer agents; polypharmacology; tyrosine kinase receptors; oncogene addiction; tumor microenvironment; FDA-approved drugs
资金
- FFR - University of Palermo grant [CUP:B78C120003-80001]
The old-fashioned anticancer approaches, aiming at arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual single target drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of a multi-target approach, the closely related evolutionary members of the tyrosine kinase family are ideal candidates. Indeed, tyrosine kinase activities are not only critical in tumor phenotype maintenance, but also modulate several functions in the tumor microenvironment. Consequently, several multikinase inhibitors were approved in the last decade, and many new molecules are currently in preclinical or clinical development. In the present review we report on the most widely FDA-approved multitargeted drugs, discussing about their mechanism of action and outlining the clinical trials that have brought them to approval.
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