Recent studies investigating the genetic determinants of cancer suggest that 
some of the genetic alterations contributing to tumorigenesis may be inherited, 
but the vast majority is somatically acquired during the transition of a normal 
cell to a cancer cell. A systematic understanding of the genetic and molecular 
determinants of cancers has already begun to have a transformative effect on the 
study and treatment of cancer, particularly through the identification of a 
range of genetic alterations in protein kinase genes, which are highly 
associated with the disease. Since kinases are prominent therapeutic targets for 
intervention within the cancer cell, studying the impact that genomic 
alterations within them have on cancer initiation, progression, and treatment is 
both logical and timely. In fact, recent sequencing and resequencing (i.e., 
polymorphism identification) efforts have catalyzed the quest for protein kinase 
'driver' mutations (i.e., those genetic alterations which contribute to the 
transformation of a normal cell to a proliferating cancerous cell) in 
distinction to kinase 'passenger' mutations which reflect mutations that merely 
build up in course of normal and unchecked (i.e., cancerous) somatic cell 
replication and proliferation. In this review, we discuss the recent progress in 
the discovery and functional characterization of protein kinase cancer driver 
mutations and the implications of this progress for understanding tumorigenesis 
as well as the design of 'personalized' cancer therapeutics that target an 
individual's unique mutational profile.