Teasing Out Mechanisms of Small-Molecule Kinase Inhibition
This article was originally published in Start Up
Even as kinases remain a popular target in oncology for industry, two recent papers show how much we have yet to learn about how to interfere with these molecules. These most recent laboratory studies help explain the confusing observation that the very act of inhibiting a kinase with a drug can also "prime" phosphorylation of that target, which in some cases can actually enhance tumor activity.
You may also be interested in...
Two independent research teams have shown that current RAF inchibitors, a class of experimental targeted cancer drugs, may only work well in patients with one particular mutation - in an enzyme called BRAF. In other people, the drugs can actually contribute to the growth of tumors. The findings echo develoments earlier in the decade with EGFr inhibitors, which proved to be harmful to some patients until the mechanism of action was worked out and their use subsequently restricted.
A group at the National Cancer Institute has shown that blocking the activity of the glycoprotein thrombospondin-1 protects surrounding tissue from the effects of ionizing radiation while, at the same time, sensitizing tumor cells to the effects of the radiation blast. The work could lead to new adjunctive cancer therapies--especially in breast cancer, to ablate residual tumor cells following reconstructive surgery.
Two years ago, a team at Stanford described a new "chemical genetics" technique--a more precise way to use small molecules to perturb gene products and living systems. Now they have published more data on the system. And of acute interest to drug developers, they have linked the work to therapeutic applications in cancer immunotherapy, showing the ability to regulate secreted proteins such as IL-2 and TNF.