In mice and laboratory cell experiments, the study, published in the journal Cancer Research, the research team sparked hope for new treatment strategies against this disease.
“This study gives us the hope of reusing common drugs for young cancer patients who desperately need better treatment options,” said study lead author Caitrín Crudden of the Karolinska Institutet in Sweden.
The study looked at the commonalities between two large groups of cell surface receptors, the so-called G protein-coupled receptors (GPCRs) and tyrosine kinase receptors (RTKs).
GPCRs are targeted by more than half of all drugs developed to treat conditions such as allergies, asthma, depression, anxiety, and hypertension, but have not been widely used to treat cancers so far.
RTKs, on the other hand, are being targeted by cancer drugs, such as breast and colon cancer, due to their implication in a variety of cellular abnormalities.
A 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 anticancer drugs against this receptor have failed.
In this study, the researchers looked at IGF1R and found that it shares a signaling module with GPCRs, meaning it may be possible to influence its function through drugs that target GPCRs.
This strategy opens up new possibilities for repurposing well-tolerated drugs to silence this tumor-driving receptor and thereby stop cancer growth.
To test their hypothesis, the researchers treated infant sarcoma cells and mouse models with paroxetine, an antidepressant drug that alters a serotonin reuptake receptor that is part of the GPCR family.
They found that this drug significantly reduced the number of IGF1R receptors on malignant cells and thus suppressed tumor growth.
The researchers also discovered the molecular mechanism behind this cross-targeting.
“We have developed a new strategy to control the activity of these tumor-guiding receptors by targeting GPCRs,” said study author Leonard Girnita of the Karolinska Institutet.
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