The specific BCR-ABL1 inhibitor molecule Glivec was the first anti-cancer drug to be developed against a tumor-specific protein. Glivec binds to the catalytic domain of BCR-ABL1 and prevents the binding of the substrate ATP, which is essential for the phosphorylation reaction catalysed by the kinase. By inhibiting the kinase activity of BCR-ABL1, Gleevec blocks the proliferation of tumor cells with Philadelphia chromosome and significantly extends the survival of the corresponding patients. Unfortunately, some tumor cells may develop resistance against Glivec mainly by point mutations in the BCR-ABL1 gene.
BCR-ABL1 and the Philadelphia chromosome – Part 1: Normal and aberrant karyograms
BCR-ABL1 and the Philadelphia chromosome – Part 2: The Philadelphia chromosome
BCR-ABL1 and the Philadelphia chromosome – Part 3: The BCR-ABL fusion protein