Pharmacogenomics and radiogenomics

In this MRFF-funded VPCC program, we will focus on identifying individual genetic risks of patients to the toxicities of cancer treatments, including chemotherapy and radiation, by applying the research principles of pharmacogenomics and radiogenomics.

Patients who are considered at high risk of toxicity to specific chemotherapy drugs could have several options, including modifying drug dose, substituting another drug or being offered an antidote. The best example is anthracycline-induced cardiotoxicity (heart damage) for which the antidote known as dexrazoxane is approved under specific clinical circumstances.

Several projects will be the focus of initial VPCC pharmacogenomics and radiogenomics research:

  1. Next generation sequencing (NGS) of DNA from patients treated for acute lymphoblastic leukaemia (ALL) who have experienced serious adverse events considered as unacceptable toxicities will identify genetic variants linked to the risk of specific toxicities. Genetic variants will then be studied in the lab towards screening drugs that can either prevent or reduce the risk.
  2. An international pharmacogenomics implementation clinical trial known as “GO-PGx” will be opened at the respective children’s cancer centres located at The Royal Children’s Hospital and Monash Children’s Hospital to assess the relative risks of: (i) heart damage from anthracycline drugs; (ii) hearing loss (ototoxicity) from cisplatin chemotherapy; or (iii) reduced bone marrow function (myelosuppression) from mercaptopurine. These drugs are used to treat several types of common paediatric cancers, including ALL, various types of sarcomas and germ cell tumours. Risk reports will be reviewed by the child’s treating oncologist and there will be discussion with the family regarding whether changes to the treatment plan will be made. We will also set up consumer-led focus groups at both Melbourne-area children’s hospitals.
  3. Children who have developed cognitive changes as a result of radiation, chemotherapy, or both will have NGS of DNA obtained from their blood to retrospectively identify those at increased risk of brain toxicity.
  4. Children who have developed second cancers as a result of radiation will have DNA from their blood and the new cancer sequenced to identify genetic risk as well as learn more about radiation-induced cancers in children.

Investigators:

Collaborators:

  • A/Prof David Elliot – Murdoch Children’s Research Institute
  • A/Prof Enzo Porrello – Murdoch Children’s Research Institute

Bioinformatics:

  • Dr Simon Sadedin – Murdoch Children’s Research Institute

The Pharmaco and Radiogenomics program is made possible thanks to generous funding from the Children’s Cancer Foundation,
the Kids Cancer Project, The Australian Cardio-Oncology Registry, and the National Heart Foundation.

Pharmacogenomics