A recent Experimental Medicine Award will allow researchers to learn more about the genetic and epigenetic causes of cancer, through an existing trial.
The ongoing DETERMINE trial aims to provide patients with rare cancers access to drugs that could target the specific genetic changes causing their cancer, even if the drug is currently only licensed for other types of cancer. New funding will take advantage of this trial to build on the work further.
Cancer Research UK have awarded a new Experimental Medicine Award to Professor Gary Middleton at University of Birmingham, who will lead the work in collaboration with colleagues at the University of Manchester, the University of Cambridge, Monash University and University of Queensland in Brisbane, to expand the trial’s remit, ensuring that a multi-disciplinary group of scientists can learn as much as possible from patients signed up to DETERMINE.
The tumour samples and subsequent blood samples taken from patients enrolled in DETERMINE and used for the new DETERMINE Translational study will be studied to better understand the genetic make-up of patients, epigenetics or genetic ageing, the immune response and how this might impact the effectiveness of treatment, as well as whether or not a treatment is working.
This wealth of data collected alongside the clinical trial will really boost the value of this work and should help in the identification of new treatments, as well as potentially being able to identify how – in molecular terms – the genetic changes driving rare cancers are triggered into action. This will hopefully allow us to therapeutically target, or inactivate, any triggers that could lead cancers to develop, even many years after the acquisition of the alteration. It will also be a valuable source of data in the search for a more precise precision medicine, one which takes into account the context in which cancer-driving mutations occur.
The existing DETERMINE trial opens up options for patients with rare cancers, beyond standard chemotherapy treatments, and will build on increasing knowledge about genetics underlying cancers. The trial includes paediatric, teenage and adult patients. Since only licensed drugs are used, side effects should be known, although these will still be monitored carefully along with changes in tumour growth to understand effects in different patient groups.
Through DETERMINE Translational, the international team aim to understand the way in which a genetic change that can cause cancer is activated by particular conditions, such as mutations, inflammation or epigenetics. Armed with this knowledge, it may then be possible to identify how to prevent certain cancers by interfering with these conditions or blocking this second triggering process.
It is hoped that the results of DETERMINE combined with DETERMINE Translational will provide new treatment options for patients with rare cancers and could help clinicians select patients more effectively in the future, avoiding treatment with ineffective medicines that might also have side effects.
Professor of Medical Oncology
Staff profile for Professor Gary Middleton, Professor of Medical Oncology in the Institute of Immunology and Immunotherapy
