IHI's Lecturer Dr Alvina Lai has had new paper published by the British Journal of Cancer
10 October 2019
“Aberrations in Notch-Hedgehog signalling reveal cancer stem cells harbouring conserved oncogenic properties associated with hypoxia and immunoevasion” published by the British Journal of Cancer
A new paper appearing as the British Journal of Cancer Monthly Top Picks led by Dr. Alvina Lai and honorary research associate Wai Chang of the UCL Institute of Health Informatics explores the Notch-Hedgehog signalling axis on cancer stem cell properties. The study employs a comparative approach to interrogate multi-modal transcript and genetic data from 21 cancer types involving over 18,000 patients.
A Notch-Hedgehog gene signature was developed, which could predict prognostic outcomes in glioma, clear cell renal cell, papillary renal cell, liver and stomach cancers. The study shows that tumours with hyperactive Notch-Hedgehog signalling have more advanced disease states where these patients also demonstrated overexpression of genes associated with stemness pathways. The study further explores the relationship between Notch-Hedgehog hyperactivation and tumour microenvironmental qualities and found associations of cancer stem cells with tumour hypoxia and immunosuppression.
The results presented in this work support a model where Notch-Hedgehog hyperactivation is linked to stemness and that hypoxia contributes to the maintenance of undifferentiated phenotypes and the reduction of anti-tumour immunity. The use of immune checkpoint blockade has been increasingly tried in malignancy. Hence, molecular signatures capable of discerning responders from non-responders will be valuable prior to the administration of these expensive drugs. The Notch-Hedgehog gene signature may serve as a staging point for exploring combinatorial treatments that simultaneously target cancer stem cells, hypoxia and tumour immunity.
To read the full paper, visit the British Journal of Cancer website.
The paper's full citation is:
Chang WH, Lai AG. Aberrations in Notch-Hedgehog signalling reveal cancer stem cells harbouring conserved oncogenic properties associated with hypoxia and immunoevasion. Br J Cancer. 2019;10.1038/s4.