Clinical-molecular factors predicting response and survival for tyrosine-kinase inhibitors.

The development of drugs with special mechanisms of action, such as tyrosine kinase inhibitors (TKIs), means that new clinical-molecular questions are being examined and this will help us to better select from the treatments available. In this study we review questions of survival and response to TKIs, attempting to distinguish prediction-and prognosis-related factors, at both the clinical and molecular levels. The evidence available today allows us to affirm that the benefits of TKI treatment occur regardless of the patient's status as a smoker, his/her gender or histological sub-type. Interestingly, in a subset analysis of ever-smokers, men with squamous cell histology derived a statistically significant survival benefit from erlotinib, a population that was previously thought not to benefit. The question of who should receive TKIs is still not completely resolved. Therefore, there should be an international effort to achieve a prognostic index, as has been done for lymphomas, that combines molecular and clinical factors. Such an index would classify patients into several sub-groups, defining the likelihood of non-response to TKIs.