An early stage therapeutic target for bile duct cancer

Bile duct cancer is difficult to detect Image © iStockphoto

Notch-3 signalling is the key driver of tumour development in bile duct cancer, with Notch-3 receptor differentially overexpressed in comparison to other notch receptors. Therapeutic targeting of this receptor could provide anti-tumorigenic effects in patients, and act as a chemotherapeutic agent with minimal side-effects.

Features   Benefits
Differentially overexpressed in comparison with other notch receptors Attractive target for anti-tumorigenic approaches and relevant as a biomarker for diagnostic purposes
Notch-3 inhibition does not interfere with the classical notch signalling pathway No off-target effects, gastro-intestinal side effects that are usually common with pan-notch inhibitors, or notch-1 inhibitors

The Challenge

Bile duct cancer (BDC) is an aggressive primary liver cancer with increasing global incidence and very poor prognosis. Current treatments provide modest effects, and surgery remains the only curative treatment. The difficulties in detecting this cancer means by the time it is diagnosed, the tumour is too advanced for surgery. There is a need for a novel therapeutic target with extensive anti-tumorigenic effects and minimal off-targets affects to treat bile duct cancer patients.

Technology

Notch signalling is crucial during development and in many forms of cancer. Researchers at the University of Edinburgh have demonstrated that Notch-3 is differentially upregulated in BDC compared to the other notch receptors and plays a key role in driving tumorigenesis. Notch-3 signalling sustains tumour cell survival through PI3k/Akt activation, a non-canonical mechanism that is independent of the classical mechanism. Therefore, specifically inhibiting Notch-3 signalling could be a means of treating BDC and avoiding the gastro-intestinal side effects that are usually seen with pan-notch inhibitors.

Exemplification Data

Surgically resected BDC tumours from human samples show differential overexpression of Notch-3 receptor compared to matched non-cancerous livers. In vivo proof of concept studies in animal models of BDC demonstrated that Notch-3 promotes tumorigenesis throughout the development of BDC. The knockdown of Notch-3 leads to reduction in tumour mass and volume and proto-oncogenes were found to be down-regulated when Notch-3 was inhibited. Further validation of the role of Notch-3 in BDC was done using primary human cell lines and ex vivo xenograft model.

Applications

  • Oncology diagnosis
  • Oncology target for drug discovery

Development Status

Animal model data

Publication

Guest et al (2016) Notch3 drives development and progression of cholangiocarcinoma

Commercial Offering

The University of Edinburgh is seeking industry partners for research collaborations (with access to a leading clinical facility).

Register your interest

If you or your company would like to find out more about this technology opportunity under Confidentiality Agreement with a view to a licence or collaborative research agreement, please complete and submit our technology enquiry form.

View technology enquiry form


We use cookies to help us make your experience on this website better. Please click the continue button to accept our cookies.
To learn more about what cookies are and how to manage them visit AboutCookies.org