Many new inhibitors of protein kinases have recently been approved for treatment of patients with cancer, but their therapeutic efficacy is often limited by rapid emergence of resistance.

Resistance against protein kinase inhibitors frequently involves secondary mutations within the kinase domain, with or without amplification of the corresponding gene.

Feedback regulatory loops often compensate for the extinguished protein kinase, thereby confer resistance to kinase inhibitors.

Identifying compensatory pathways able to confer resistance to kinase inhibitory drugs might translate to novel combination treatments.

Other strategies able to circumvent resistance involve introduction of second and third generation kinase inhibitors, as well as antibody mixtures and other agents.