Kinase inhibitors (TKIs)

Many cancers grow because a signaling protein called a kinase is permanently switched on, most often as the result of a genetic change in the tumor. The kinase keeps sending "divide" signals down a chain of proteins inside the cell. Kinase inhibitors are molecules small enough to enter the cell and fit into the kinase, blocking the site it needs to pass the signal on. With the signal interrupted, the cancer cells stop dividing or die. A well-known example is imatinib, which the NCI lists for Philadelphia-chromosome-positive chronic myeloid leukemia and for GIST tumors with an abnormal KIT protein, among other uses. Because each inhibitor matches a specific kinase, tumors are tested for the relevant abnormality (biomarker testing) before treatment. Cancer cells can, however, acquire new mutations that change the kinase's shape — one reason resistance to these drugs can develop.