Drugs don’t always behave exactly as expected. While researchers may develop a drug to perform one specific function that’s perhaps tailored to work for a specific genetic profile, sometimes the drug might perform several other functions outside of its intended purpose.
This concept of drugs having multiple functions, called polypharmacology, may lead to unintended consequences. This is a common occurrence for cancer drugs in clinical trials that can have harmful side effects and treatment toxity.
But polypharmacology may in fact be the norm for most drugs, not the exception. So rather than seeing a drug’s ability to perform many functions as a flaw, biomedical data scientists like me and my lab colleagues believe that it can be used to our advantage in designing drugs that address the full complexity of biology.
Drugs often multitask in cells
When scientists talk about drugs, they like to refer to its mechanism of action, or MOA – essentially, exactly what a drug does when it enters the body. A drug’s official MOA, however, may not actually include all the ways it can affect cells.
For example, the mechanism of action of a drug labeled as a VEGF inhibitor is to block the activity of a protein called VEGF, or vascular endothelial growth factor, in a cell. While VEGF plays an important role making new blood vessels, a process that’s integral to healthy tissue development, it can also be a hallmark of cancer. Blocking VEGF can stop the formation of new blood vessels that supply nutrients to tumors and prevent the growth and spread of many types of cancers.
There are currently 14 drugs inhibiting new blood vessel formation approved in the U.S. to treat cancer, and most target VEGF. You may be wondering why there are so many different drugs available if they’re all inhibiting the same protein. The answer comes down to polypharmacology: While they all most likely work by blocking VEGF in some way, each likely has some other function that may be unique to that drug. That alternative function might cause side effects, or only work in certain conditions.
VEGF belongs to a larger group of proteins called receptor tyrosine kinases, or RTKs, that are challenging to target individually. Many drugs that target one type of RTK, like VEGF, also end up indiscriminately targeting other RTKs because they share a similar chemical structure, potentially causing unwanted side effects.
For example, in 1999, scientists discovered that the infamous morning sickness drug thalidomide also worked as a VEGF inhibitor to treat multiple myeloma, a type of blood cancer. This was a triumph for a drug that, just 70 years prior, was banned worldwide after causing severe birth detects in an estimated 10,000 infants, not including miscarriages and stillbirths.