In summary, multi-TK inhibitors are being designed to target multiple activated kinases. The future design plan for these compounds should take into consideration the activated array of kinases in a given tumor. This undoubtedly will increase the efficacy, also avoiding toxicity. Furthermore, irreversible TK inhibitors show more efficacy than reversible ones, with a similar toxicity profile, thereby presenting these inhibitors as attractive alternatives to reversible inhibitors. In addition, irreversible inhibitors may offer advantages with respect to their ability to be more efficacious to fight avoid resistance due to secondary mutations. The development of multikinase, reversible, irreversible, and other allosteric inhibitors of tyrosine kinases is clearly widening the armamentarium to fight neoplastic diseases, and will allow better targeting of the tumoral cells, improved toxicological properties, and more favourable responses by preventing drug resistance.

Grant Support: AO receives support from the Spanish Association Against Cancer (AECC) and from the FISCAM grand program PI-2007/41.

Peer Reviewed