Study finds key molecule that fuels the transformation of some prostate and lung cancers into more aggressive forms

A new study by a team of Toronto-based researchers partly funded by the Marathon of Hope Cancer Centres Network has revealed that a specific type of circular RNA (circRNA) plays a crucial role in transforming some prostate and lung cancers into more aggressive, treatment-resistant forms of the disease. The study, published in Cancer Cell, also highlights that targeting this specific circRNA could have potential therapeutic benefits for patients.

Led by Dr. Housheng (Hansen) He from the Princess Margaret Cancer Centre, the team sought to uncover why some prostate and lung adenocarcinomas transform into more aggressive types of cancer called neuroendocrine prostate cancer (NEPC) and small cell lung cancer (SCLC), which are hard-to-treat tumours that grow on neuroendocrine cells.

Using gene expression analysis, the team found that a specific circRNA, known as circRMST, promotes the transformation of prostate and lung adenocarcinomas into NEPC and SCLC by interacting with two key proteins called SOX2 and NKX2-1, which in turn promote the expression of a gene called ASCL1 that drives the development of neuroendocrine cells.

These finding shed new light on the key role of circRMST in the progression of prostate and lung adenocarcinoma and reveals circRMST as a potential target for therapeutic strategies aimed at preventing the development of neuroendocrine tumours.

This story is prepared from an article originally published by the University Health Network.

Study

Teng M, Guo J, Xu X, Ci X, Mo Y, Kohen Y, Ni Z, Chen S, Guo WY, Bakht M, Ku S, Sigouros M, Luo W, Macarios CM, Xia Z, Chen M, Ul Haq S, Yang W, Berlin A, van der Kwast T, Ellis L, Zoubeidi A, Zheng G, Ming J, Wang Y, Cui H, Lok BH, Raught B, Beltran H, Qin J, He HH. Circular RMST cooperates with lineage-driving transcription factors to govern neuroendocrine transdifferentiation(link is external). Cancer Cell. 2025 May 12. doi: 10.1016/j.ccell.2025.03.027. Epub 2025 Apr 17.

Funding

This study is partly funded by the Network funding to Dr. Housheng Hansen He as part of the Princess Margaret Cancer Consortium’s Canadian Prostate Cancer Genome Project.