Tyrosine Kinase Inhibitors in Cancers: treatment optimization - Part I.

A multitude of TKI has been developed and approved targeting various oncogenetic alterations. While these have provided improvements in efficacy compared with conventional chemotherapies, resistance to targeted therapies occurs. Mutations in the kinase domain result in the inability of TKI to inactivate the protein kinase. Also, gene amplification, increased protein expression and downstream activation or bypassing of signalling pathways are commonly reported mechanisms of resistance. Improved understanding of mechanisms involved in TKI resistance has resulted in the development of new generations of targeted agents. In a race against time, the search for new, more potent and efficient drugs, and/or combinations of drugs, remains necessary as new resistance mechanisms to the latest generation of TKI emerge. This review examines the various generations of TKI approved to date and their common mechanisms of resistance, focusing on TKI targeting BCR-ABL, epidermal growth factor receptor, anaplastic lymphoma kinase and BRAF/MEK tyrosine kinases.

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Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest CL has benefitted from assistance from BMS, MSD, Novartis, Amgen, Roche, Avantis Medical Systems, Pierre Fabre, Pfizer and Incyte. NM declare has benefited from assistance from BMS, MSD, Novartis, Pierre Fabre, Sanofi, Merck and Sun Pharma. FF declare the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.