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Research projects underway

CHECT funded retinoblastoma research

These projects are currently being funded by CHECT. For past research please have a look at our previous retinoblastoma research page.

Developing an evidence-based psycho-educational intervention for teenagers and young adults who have had retinoblastoma

Project leader Dr Bob Phillips
Award £73,799
Duration three years, October 2020 

Summary 

There is little guiding evidence about the specific challenges that teenagers who have had retinoblastoma face as they transition towards young adulthood. Understanding the psycho-educational needs of teenagers and young adults as they transition into adulthood is therefore essential if we are to offer effective interventions to support them. This PhD studentship aims to develop an evidence-based intervention for teenagers and young adults with retinoblastoma that offers relevant, accessible and effective psycho-educational support.

Status: on hold

Comparing blood to aqueous humor as a liquid biopsy for retinoblastoma: determining the superiority of the aqueous humour as a source of tumor DNA

Project leader Professor Jesse Berry
Award £50,000
Duration two years, December 2019

Summary

A liquid biopsy for retinoblastoma is especially critical because unlike other cancers, retinoblastoma cannot be biopsied due to risk of spread outside the eye. To overcome this problem, this team has demonstrated that tumor DNA is present in the aqueous, the clear fluid in front of the eye, which is safe to extract. However, the question remains whether blood, which is less invasive, can be used as a liquid biopsy for retinoblastoma as it can with other cancers. The team aims to directly compare blood to aqueous to determine which is a superior source of tumor DNA and thus a better liquid biopsy for retinoblastoma. This critical research has potential to change paradigms of diagnosis, prognosis and future treatment protocols for affected children.

Status: on hold 

Assessing the feasibility of pluripotent stem cell derived retinal organoids as a model system to test the safety and efficacy of chemotherapeutic agents in retinoblastoma

Project leader Professor Majlinda Lako
Award £50,000
Duration 18 months, May 2020

Summary 

The recent advances in local delivery of chemotherapy to the eye (intra-arterial or intravitreal injection) have significantly improved the success of eye conserving treatment, with reduction in the need for enucleation. However, there is inevitably some toxicity associated with treatment, which can affect visual function in the eyes that are saved. Further refinements in these techniques and trials of new drugs are essential to maximise efficacy and minimise toxicity, to preserve useful vision. The recent development of retinal organoids by our group provides us with a unique laboratory model of human retina and retinoblastoma. This study is designed to test the safe and effective dose of current as well as novel drugs on the laboratory model (retinal organoids), and to study the toxic effects on the retina. This valuable information will help shape treatment strategies such as new drug combinations and new dosage schedules to treat effectively retinoblastoma tumours while minimising damage to vision.

Status: on hold

Next generation sequencing analysis of retinoblastoma samples

Project leader Professor Shin-Ichi Ohnuma
Award £55,000
Duration 18 months, March 2019

Summary

Despite knowing the RB1 mutation it is difficult to predict the outcome of treatment. This project proposes to study the  genetic changes that occur in retinoblastoma, using whole genome sequencing (the process of determining the complete DNA sequence) to detect those variants associated with good and bad prognosis or with a favourable treatment outcome. This new level of diagnosis could potentially make a significant contribution to the selection of treatment, and avoid the loss of one or both eyes. Also, identification of new cancer modifying genes may provide new targets for treatment. Furthermore, this study aims to establish a new system to diagnose Rb in the clinical setting, which includes detailed examination of patient genome sequencing/analysis.

Status: In progress

Eloise Patterson Project

Project leader Dr Zerrin Onadim
Award Phase I £24,800; Phase II 24,978.39
Duration Phase I one year, Nov 2015; Phase II one year December 2020

Summary

Records held at the Royal London Hospital will be studied alongside those from the Childhood Cancer Research Group to investigate the way in which risk of tumours occurring in later life depends on different genetic mutations associated with heritable Rb, on the treatment (radiotherapy, chemotherapy) used in treating Rb, and to calculate statistical estimates of these risks.

It is hoped this will lead to clinicians and geneticists having better information available to them when assessing the risks of second tumours occurring. This could potentially lead to earlier diagnosis and treatment of these second cancers.

Status: Phase II commencing December 2020

Investigation of the mutational landscape of retinoblastoma

Project leader: Dr Carmel McConville
Award: £15,000 joint funding CHECT and Fight for Sight; additional £14,200 CHECT
Duration: One year, May 2014
Extension funding awarded: £6,500 CHECT
Duration: 14 months, November 2018

Summary

We have established cell lines from 15 different retinoblastomas and these represent one of the largest collections of retinoblastoma cell lines worldwide.

We will use the latest technology, known as ‘next generation sequencing’, to look at the DNA sequence of every active gene in these retinoblastoma cell lines. This sequence will be compared to a normal reference sequence in order to identify genes which are mutated. The sequence analysis will indicate which genes which are most frequently mutated in retinoblastoma and will also show how the overall cellular genetic activity is influenced by these mutated genes.

All of this information is essential to inform future research into the development of novel targeted therapeutics capable of reversing the effects of mutated genes in retinoblastoma.

Status: Project extension commenced November 2018

Modelling retinoblastoma using human induced pluripotent stem cells (iPSC)

Project leader Dr Sandy Hung
Award £34,315
Duration 18 months, June 2015

Summary

It has been a challenge to develop a good cell model system for retinoblastoma (Rb), despite it being the first cancer to have its gene identified. Model systems are important tools which enable scientists to better understand the diseases and develop more effective treatments. However, current models for RB (e.g. mouse), cannot accurately reproduce what is observed in RB patients due to differences in disease mechanisms between species.

This project proposes to make induced pluripotent stem cells (iPSCs) from skin cells of Rb survivors with known heritable Rb mutations, to make different cell types, including the retinal (eye) cells that become cancerous in Rb. Ultimately, this model system could enable researchers to test potential treatments. A successful human Rb model would also, in the future, enable researchers to gain insight into the development of second cancers commonly seen in Rb survivors.

Status: In progress

Autonomic reflexes and cardio-respiratory instability during super-selective intra-arterial chemotherapy in the management of children with retinoblastoma

Project Leader: Dr S P McGuirk et al. at Great Ormond Street Hospital and Birmingham Children’s Hospital.
Award: £18,000
Duration: One year from May 2014.

Summary

Previous studies have reported that intra-arterial chemotherapy is a safe and effective treatment in children with advanced disease. It causes complete regression of the tumour and preservation of vision in most cases. However, we have observed that a significant proportion of children developed severe adverse cardio-respiratory responses during the procedure. These reactions have occurred only during the second catheterisation procedure and are characterised by the sudden development of acute bronchospasm, impaired ventilation and marked haemodynamic instability.

Patients have been resuscitated with intravenous fluids, intravenous atropine and intramuscular epinephrine with rapid restoration of normal cardio-respiratory function. None of the children had any adverse sequelae following these events.

We do not currently understand why these responses occur, why they occur in some children but not others, or why they are only clinically evident during the second catheterisation procedure. We believe that they represent an autonomic reflex response, which is qualitatively similar to the trigemino-cardiac and trigemino-respiratory reflexes observed during corrective surgery for strabismus, cranial and maxillofacial surgery, and skull base surgery.

We propose to undertake this prospective case-controlled study to examine the pathophysiological events in detail. In particular, this study will determine the incidence of the trigemino-cardiac and trigemino-respiratory reflexes and quantitatively measure the effect of these reflex responses on haemodynamic and respiratory function. Ultimately, this information may allow us to identify adverse responses before they become clinically apparent, thus improving the safety of this procedure. The findings of this study are, therefore, of potentially immediate clinical application.

Status: In progress. See the following article in Pediatric Anesthesia.