The oxytocin receptor signalling system in breast cancer: what we know and what we don’t know

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Breast cancer is a major threat to female health worldwide. Hormones play a critical role in breast cancer development and progression, and emerging evidence also points to an involvement of the peptide hormone oxytocin (OT) and its G protein-coupled receptor, the oxytocin receptor (OTR). Centrally, the OT/OTR signalling system regulates complex social behaviour, and, peripherally, it plays an essential role during labour and breastfeeding. In the last few decades, the OT/OTR signalling system has gained more and more attention in breast cancer research due to its association with protective effects against breast cancer development.

In the 1990s, the concept of OT’s preventive potential against breast cancer was discussed and reviewed for the first time [1], and OTR was later found to be widely expressed in human breast carcinomas both in cell lines and breast cancer tissue. However, little is known about the mechanistic role of OT/OTR during breast cancer development and progression. The complexity and research gaps regarding the molecular biology of OTR signalling in breast cancer makes it challenging to clarify which pathways could be targeted to improve breast cancer management. We therefore decided that a critical review highlighting the gaps in current knowledge and providing guidance towards future research efforts would be timely and valuable to advance our understanding of OT/OTR’s role during breast cancer development and progression.

In our recent review published in Oncogene, we provide a comprehensive and up-to-date overview of OT/OTR signalling in breast cancer. We looked at OTR signalling in the normal breast as well as in breast cancer and tried to identify which pathways are particularly relevant for breast cancer development or prevention. Many of the signalling studies of the OT/OTR system have however been carried out in different cell systems other than normal breast or breast cancer cells, and we are still far away from having OTR drug candidates suitable for clinical studies, despite the efforts taken in this field. Broader and more systematic studies are required to define the therapeutic potential of OTR in breast cancer management. Nevertheless, we hope that this review provides a clear overview of the status quo of the field and that it will inspire others to join us in investigating the OT/OTR system in breast cancer, which we consider a promising target for breast cancer diagnosis and treatment that is worth pursuing.

Reference

1. Murrell TG. The potential for oxytocin (OT) to prevent breast cancer: a hypothesis. Breast Cancer Res. Treat. 1995; 35: 225-229.

Markus Muttenthaler

Professor, University of Vienna

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