Researchers found that a commonly used antidepressant could treat childhood cancer – successfully stopping growth in lab experiments so far
Childhood sarcomas are aggressive tumours that develop in bone or soft tissue, like muscles, tendons and connective tissues. They are often treated with combinations of surgery and intensive radio- and chemotherapy that carry substantial short and long-term toxicities. Survival and relapse rates have not improved in decades, meaning that novel treatment options are crucially necessary – fiercely creative innovation is the way to improve the lives of children with sarcomas.
This study is undertaken by researchers at Karolinska Institutet in Sweden and MD Anderson Cancer Centre in Texas, published in the journal Cancer Research.
How can an antidepressant be used against cancer?
The study examined similarities between two large groups of cell surface receptors, the so-called G protein-coupled receptors (GPCRs) and the receptor tyrosine kinases (RTKs). GPCRs are targeted by more than half of all developed drugs to treat conditions such as allergies, asthma, depression, anxiety and hypertension – but up until now, they haven’t really been considered by cancer treatments.
RTKs, on the other hand, are targeted by drugs against cancers, such as breast and colon cancers, due to their implication in a variety of cellular abnormalities. One receptor in the RTK family that plays a key role in many cancers is the insulin-like growth factor receptor (IGF1R). However, previous attempts to develop anti-cancer drugs against this receptor have failed – including every attempt to fight this receptor in childhood sarcomas.
In this study, the researchers scrutinised 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, essentially stopping the cancer from growing any further.
Using Paroxetine, the research team focused on mice and cells
To test their idea, 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. Mice and laboratory cell experiments showed that Paroxetine actually decreased the number of IGF1R receptors and suppressed the cancer growth as a whole.
“We have developed a novel strategy to control the activity of these tumour-driving receptors by striking the GPCRs,” says Leonard Girnita, researcher in the Department of Oncology-Pathology, Karolinska Institutet, and principle 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.”
‘It gives us hope’
The study’s first author, Caitrín Crudden, a former PhD student in the receptor signaling 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.”
The next step for this discovery will be replicating these results in a clinical setting.