A commonly prescribed antidepressant may prevent the growth of childhood cancer.
The findings for the treatment of childhood, or Ewing, sarcoma were discovered in a study of mice and laboratory cell experiments by researchers at Karolinska Institutet in Sweden and Texas' MD Anderson Cancer Centre.
“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,” first author, Caitrín Crudden, former Ph.D. student in the receptor signaling pathology group at the Department of Oncology-Pathology at Karolinska Institutet, said in a statement.
In the study, which was published in the journal “Cancer Research,” scientists explored commonalities between two large groups of cell surface receptors: the “G protein-coupled receptors” (GPCRs) and the receptor tyrosine kinases (RTKs). Over half of all developed medications target GPCRs to manage conditions including depression, anxiety, hypertension allergies and asthma. However, they have not been used extensively to treat cancers thus far.
By contrast, drugs target RTKs against cancers — including breast and colon cancers — due to their involvement in a variety of cellular anomalies. The insulin-like growth factor receptor (IGF1R) is an RTK receptor that plays a pivotal role in many cancers, including childhood sarcoma. Still, past efforts to develop anti-cancer drugs against this receptor have failed.
Researchers examined IGF1R and discovered a shared signaling module with the GPCRs. That indicates the possibility for it to affect its function through drugs targeting the GPCRs. This approach offers possibilities of repurposing well-tolerated drugs to quell this tumor-driving receptor and inhibit cancer growth.
Researchers tested their hypothesis by treating childhood sarcoma cells and mouse models with Paroxetine, which is part of the GPCR-family. It is an anti-depressant drug that impairs a serotonin reuptake receptor. They found that this drug notably reduced the number of IGF1R receptors on the malignant cells. As such, it stifled the tumor’s growth.
“We have developed a novel strategy to control the activity of these tumour-driving receptors by striking the GPCRs,” researcher in the Department of Oncology-Pathology, Karolinska Institutet, and lead study investigator Leonard Girnita said in a statement. “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.”
Researchers will next verify their findings in a clinical setting.
According to St. Jude Children’s Research Hospital, Ewing sarcoma is very rare and is the second most common type of bone cancer in children. Annually, around 200 children and young adults are diagnosed with Ewing sarcoma in the U.S.
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