Resistance to antineoplastic therapy. The oncogenic tyrosine kinase-Bcl-x(L) axis

The discovery two decades ago that the Philadelphia chromosome encodes an oncogenic fusion of Bcr and Abl remains among the most important contributions to our understanding of the process of malignant transformation. We now know that Bcr-Abl is one of more than 30 aberrantly activated tyrosine kinases that are expressed in a variety of tumors. Conventional treatment of the tumors in which these proteins are expressed is usually doomed to failure because the activated tyrosine kinases render the tumor cells stubbornly resistant to apoptosis. In this context, it is notable that Zhao and coworkers have uncovered a novel weapon in the resistance armamentarium of these rogue kinases, the suppression of the inactivating deamidation of Bcl-xL (this issue of Cancer Cell).