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.
Next generation sequencing analysis of retinoblastoma samples
Project leader Professor Shin-Ichi Ohnuma
Duration 18 months, March 2019
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
Duration One year, Nov 2015
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: In progress
Modelling retinoblastoma using human induced pluripotent stem cells (iPSC)
Project leader Dr Sandy Hung
Duration 18 months, June 2015
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.
Duration: One year from May 2014.
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.