Researchers from Sweden and the US have found that a commonly prescribed antidepressant may help stop the growth of a cancer known as childhood sarcoma, a disease in which cancer cells form in soft tissues of the body.
In their study, the researchers looked at commonalities between two large groups of cell surface receptors. The first is known as G protein-coupled receptors (GPCRs) and is targeted by more than half of all developed drugs to treat conditions including allergies, depression, and hypertension. Until now, however, they have not been targeted to treat cancer.
The second group of cell surface receptors is known as receptor tyrosine kinases (RTKs). These receptors are currently targeted by drugs to treat various cancers, including breast and colon cancer, due to their involvement in a variety of cellular abnormalities. One receptor in this group, known as a insulin-like growth factor receptor (IGF1R), is known to play a key role in a variety of cancers. While some have attempted to use it as a drug target, none have so far succeeded.
In this study, however, the researchers found that IGF1R shares a signaling module with GPCRs. This means that drugs that target GCPRs may be able to affect its function. As such, the researchers decided to repurpose an existing drug to see how it may affect cancer growth.
In the end, they decided to treat mice infected with childhood sarcoma cells with Paroxetine, an antidepressant that impairs a serotonin reuptake receptor that is a part of the GPCR-family. In doing so, they found that the drug was able to reduce the number of IGF1R receptor cells on the malignant cells, and thus suppress tumor growth.
"We have developed a novel strategy to control the activity of these tumor-driving receptors by striking the GPCRs," says Leonard Girnita, principal investigator of the study.
"To our knowledge this represents a new paradigm for the entire class of cancer-relevant RTKs and could be used as a starting point for the rational design of specific therapeutics in virtually any pathological conditions. This is especially important considering the huge number of GPCR-targeting medicines already in clinical use and with low toxicity."
The researchers now hope to develop their strategy to selectively cross-target multiple RTKs to treat cancer. They then hope to test their findings in clinical trials.