A new study has found that a common anti-depressant may stop the spread of childhood sarcoma in mice and laboratory cell experiments.
The findings, from researchers at Karolinska Institutet, Sweden, and MD Anderson Cancer Centre, USA, were published in the journal Cancer Research. The study examined commonalities between two large groups of cell surface receptors, G protein-coupled receptors (GPCRs) and the receptor tyrosine kinases (RTKs), to determine how to efficiently combat the spread of childhood sarcoma.
GPCRs are targeted by more than half of all developed drugs to treat conditions such as allergies, asthma, depression, anxiety, and hypertension, but have so far not been widely used to treat cancers.
RTKs are targeted by cancer drugs 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).
The study’s first author, Caitrín Crudden, a former PhD student in the receptor signalling pathology group at the Department of Oncology-Pathology at Karolinska Institutet, said: “Although this study was done in 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.”
In this study, the researchers examined the IGF1R and 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 strategy opens new possibilities of repurposing well-tolerated drugs to silence this tumour-driving receptor and thereby halt cancer growth.
To test their hypothesis, the researchers treated childhood sarcoma cells in mice 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 malignant cells and thereby suppressed the growth of the tumour. The researchers also uncovered the molecular mechanism behind this cross-targeting.
Leonard Girnita, a researcher in the Department of Oncology-Pathology, Karolinska Institutet, and principle investigator of the study, said: “We have developed a novel strategy to control the activity of these tumour-driving receptors by striking the GPCRs. 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.”