Cancer Res: Scientists hope to redirect antidepressants to treat childhood cancer

NOVEMBER 16, 2020 // -- In a recent study published in the international journal Lancer Research, scientists from the Caroline Institute in Sweden and other institutions found that a commonly used antidepressant drug may slow the growth and progression of childhood sarcoma through experiments in mice and laboratory cells, and the results are expected to help develop new targeted therapies for childhood cancer.
'Although this study was conducted in mice, and we don't know if the results can be applied to the human body, it gives us the idea of reorienting common drugs so that they can be used in young cancer patients who are currently in urgent need of new therapies,' said lead author Caitrín Crudden. In the
article, the researchers analyzed the commonality of two large cell surface receptors, G PROTEIN coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs), which can be targeted by more than half of drugs to treat diseases such as allergies, asthma, depression, and high blood pressure, but have so far not been developed to treat human cancer.
RTKs, because of its involvement in the occurrence of multiple cellular abnormalities, can be targeted by drugs that fight cancer, such as breast and colon cancer, and a receptor in the RTK family plays a key role in a variety of cancers, including childhood sarcoma, called insulin-like growth factor receptors (IGF1R), after researchers tried unsuccessfully to develop anti-cancer drugs that act on the receptor.
Photo Source: In the Pixabay/CC0 Public Domain study, researchers conducted an in-depth analysis of IGF1R and found that IGF1R was able to share a signal module with GPCRs, which means that it may be able to influence its function by targeting drugs that act on GPCRs, a strategy that may provide researchers with the idea of redirecting better-resistant drugs to silence tumor-driven subjects and slow cancer growth.
To test this hypothesis, the researchers used the drug paroxetine, an antidepressant that damages serotonin reuptake ligands (GPCR families), to treat childhood sarcoma cells and mouse models, and found that the drug significantly reduced the number of IGF1R subjects on the surface of malignant cells, thereby inhibiting tumor growth, and they also uncovered the molecular mechanisms behind this cross-targeting effect. 'Now that we've developed a new strategy to control tumor-driven receptor activity by targeting GPCRs,' said
researcher Leonard Girnita, "as far as we know, this study represents a new paradigm for research across the cancer-related RTKs category and is expected to serve as a new research starting point to help researchers design special treatments under almost any case condition, which is critical for the later development of a large number of less toxic targeted GPCR drugs used in clinical practice.'
next step researchers plan to develop new strategies to selectively cross-target a variety of RTKs and confirm this result in clinical studies.
original source: Caitrin Crudden, Takashi Shibano, Dawei Song, et al. Addion of G protein-coupled receptor kinase 2 promotes unbiased downregulation of IGF-1 receptor and orders malignant cell growth. Cancer Research (2020). DOI:10.1158/0008-5472.CAN-20-1662