Researchers have found that a commonly prescribed anti-depressant may impede the development of childhood sarcoma, a type of cancer.
Researchers at the Karolinska Institutet in Sweden and MD Anderson Cancer Centre in Texas carried out the laboratory cell experiments on mice to understand the effect of the anti-depressant on cancerous cells.
The study was published in the journal Cancer Research.
The study’s first author, Caitrin Crudden, a former Ph.D. student in the receptor signalling pathology group at the Department of Oncology-Pathology at Karolinska Institutet, said: “Although this study was done on mice and we do not yet know how translatable the results are to humans, it gives us hope for repurposing common drugs for young cancer patients desperately requiring better treatment options.”
For the study, researchers analysed similarities between two large groups of cell surface receptors, the so-called G protein-coupled receptors (GPCRs) and the receptor tyrosine kinases (RTKs).
The GPCRs are treated by drugs developed for various health conditions, including allergies, asthma, depression, anxiety and hypertension. However, these have not been used as a treatment for cancer so far.
The RTKs are targeted by drugs against cancers in the breast and colon due to their implication in a variety of cellular abnormalities.
One receptor in the RTK family that plays a key role in many cancers, including childhood sarcoma, is the insulin-like growth factor receptor (IGF1R). However, previous attempts to develop anti-cancer drugs against this receptor have failed.
In this study, the researchers examined the IGF1R. They found that it shares a signalling module with the GPCRs, meaning it may be possible to affect its function through drugs targeting the GPCRs.
This observation opens new doors to prevent the tumour-driving receptor to impede cancer growth.
To test their hypothesis, the researchers treated childhood (Ewing) sarcoma cells and mouse models with Paroxetine, an anti-depressant drug that impairs a serotonin reuptake receptor that is part of the GPCR-family.
They found that this drug significantly decreased the number of IGF1R receptors on the affected cells and thereby prevented the growth of the tumour. The researchers also uncovered the molecular mechanism behind this cross-targeting.
Lead investigator of the study, Leonard Girnita, a researcher in the Department of Oncology-Pathology, Karolinska Institutet, said: “We have developed a novel strategy to control the activity of these tumour-driving receptors by striking at the GPCRs.”
He added: “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 condition. This is especially important considering the huge number of GPCR-targeting medicines already in clinical use and with low toxicity.”