Therapeutic potential of new tumour suppressor, PRELP, in retinoblastoma

Research details

  • Type of funding: PhD Studentship
  • Grant Holder: Professor Shin-ichi Ohnuma
  • Institute: University College London (UCL)
  • Region: London
  • Start date: October 2018
  • End Date: March 2022
  • Priority: Treatment
  • Eye Category: Ocular cancer
Retinoblastoma is the most common childhood cancer of the eye (incidence 1 in 15,000 live births, 40-50 new cases a year in the UK). Retinoblastoma is aggressive but curable when diagnosed early. However, if it is not treated promptly, it can spread beyond the eyes to other parts of the body and become life-threatening. A significant number of patients need to undergo the removal of one or both eyes because there is no other suitable treatments.

Evidence shows that a secreted protein called PRELP contributes to retinoblastoma progression. The expression of PRELP is strongly suppressed in human retinoblastoma. When the expression is suppressed in a mouse retina, it results in abnormal retinal structures. Moreover, its activation in retinoblastoma cells suppresses the progression of cancer in cell culture.

PRELP has the ability to suppress the growth of other cancers and increase their sensitivity to chemotherapy. These observations suggest that the application of PRELP into an eye with retinoblastoma may inhibit the progression of cancer.

The aim is to examine the effect of the secreted protein PRELP on the progression of retinoblastoma. How it influences the properties of retinoblastoma, including its aggressiveness and sensitivity to chemotherapy will be investigated. Novel approaches to retinoblastoma treatment will also be examined.

The molecular mechanisms and effects of PRELP application to cells derived from retinoblastoma samples on cell proliferation and any cancer related phenotypes will be analysed.

A retinoblastoma animal model will be created through injections of human retinoblastoma cells to mouse eyes and examine the effects of PRELP application to its development. Whether PRELP application reduces retinoblastoma progression and the sensitivity of retinoblastoma to chemotherapy will be examined.

This project will determine the potential suitability of the protein PRELP for the treatment of retinoblastoma. It will provide novel insights into the development of new therapeutic approaches and drugs for the treatment of retinoblastoma and will provide scientific background for new diagnostic approaches based on the expression of the secreted protein.