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Kinase inhibitors in multitargeted cancer therapy

Gentile, Carla, Martorana, Annamaria, Lauria, Antonino and Bonsignore, Riccardo ORCID: https://orcid.org/0000-0003-2699-4384 2017. Kinase inhibitors in multitargeted cancer therapy. Current Medicinal Chemistry 24 (16) , pp. 1671-1686. 10.2174/0929867324666170112112734

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Abstract

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 singletarget 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.

Item Type: Article
Status: Published
Schools: Chemistry
ISSN: 1875-533X
Date of Acceptance: 25 November 2016
Last Modified: 07 Nov 2022 09:19
URI: https://orca.cardiff.ac.uk/id/eprint/128681

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