New markers and treatment targets in retinoblastoma
Research type
Research Study
Full title
Identification of new mechanisms and targets in retinoblastoma: a cohort study using fresh tissue samples for in vitro studies, leading to novel in vivo imaging techniques and treatment strategies
IRAS ID
106919
Contact name
Mandeep Sagoo
Contact email
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Retinoblastoma (RB) is the commonest inherited childhood cancer and accounts for approximately 11% of cancers developing in the first year of life. Untreated, RB is invariably fatal. The first aim of treatment is to save the child’s life; the second aim is to save the affected eye and vision.
The primary cause of RB are mutations in the Rb1 gene. These mutations allow tumours to form inside the eye, but we do not know all the steps from the first mutation to the development of tumours.
There are two main forms of RB: inherited and sporadic. Children with the inherited form usually develop tumours in both eyes, and have a high risk of developing other cancers later in life, particularly osteosarcoma and soft tissue tumours. These secondary tumours are often fatal. Sporadic RB usually affects one eye only, but often presents late, with advanced tumours requiring enucleation.
The Small Leucine Rich Proteoglycans (SLRP) are a family of 15 proteins. SLRP levels are abnormally low (downregulated) in cancers affecting organs other than the eye, including osteosarcoma.
We have conducted an exploratory study of RB cell lines and have observed that some SLRP are downregulated. We now need to confirm whether this is also true in primary cancer cells from fresh tissue samples.
Our second research question is whether RB contains cancer stem cells (CSC), which may explain why some tumours respond poorly to treatment. CSC have been observed in human RB tissue, and we will explore whether they can be manipulated to lose their stem cell properties, making them more vulnerable to treatment.
Our third research question is to identify new gene mutations that function as diagnostic factors/progression factors and modifying genes that regulate efficacy of RB treatment by bio-statistical examination of whole genome sequence data, epigenetic sequence data, and expression profiling of RB patient samples.
REC name
London - Hampstead Research Ethics Committee
REC reference
15/LO/0647
Date of REC Opinion
8 Apr 2015
REC opinion
Favourable Opinion