How do drugs target specific signal transduction pathways and alter cellular response?

1 Answer
Dec 5, 2016

Drugs usually target one particular molecular target (i.e., protein) in a particular signaling cascade. Most drugs inhibit these proteins, although a very few select drugs activate them.


Over the last fifteen years as better genetic sequencing and bioinformatics techniques makes it easier to identify proteins (often in signaling cascades) which are inappropriately active/inactive in particular disease states, so a lot of drugs have been developed to target these pathways.

The classic example is cancer and chemotherapies that target particular molecules in particular diseases.

Receptors on the outsides of cells are particularly attractive targets in signaling pathways because the drug molecules can bind to extracellular domains - researchers don't need to find ways to get the drug into the cells. The EGFR inhibitor cetuximab is a classic example - it binds, inhibits Ras-Raf-Myc signaling in a lot of epidermoid carcinomas, and sometimes prolongs life and/or improves prognoses.

Intracellular signaling is subtle, riddled with feedback loops and cross talk - the knee jerk one-protein-one-inhibitor mentality almost invariably doesn't work. Most successful chemotherapy regimens these days involve multiple cellular inhibitors against multiple over-active pathways given in combination.