This year, about 1000 children and adolescents in Australia will have been diagnosed with cancer and 5600 will have continued their treatment. Any cancer diagnosis, for yourself or a loved one, is heart-wrenching. For children, who have a lot of life to live, it seems profoundly unfair.
But, what if we could literally stop cancer in its tracks? This is the ultimate goal of researchers at the Institute who study biological pathways associated with cancer.
Dr Jason Cain’s laboratory investigates lung cancer and paediatric cancers including brain tumours, to develop new treatments with fewer side effects. The team is specifically interested in studying the most insidious cancer types with low survival rates.
Dr Cain’s laboratory’s latest world-first discovery – in developmental and small cell lung cancer (SCLC) models – has implications for childhood cancer, with further research findings slated for publication. Thanks to your generous support funding this research, the team recently discovered two potential genetic markers that could be used to provide more personalised cancer treatments.
“This discovery could help us learn which patients, and which tumours, are likely to respond to an emerging cancer therapy,” said Dr Cain, Head of the Developmental and Cancer Biology Research group.
The team discovered that changes in two genes, TP53 and RB1 (which act as tumour suppressors), played a role in activating a developmental pathway called Hedgehog signalling, which is associated with a wide range of cancers.
These two genes could act as genetic biomarkers in tumours that are likely to respond to new cancer treatment drugs, known as Hedgehog inhibitor therapies. Many of these drugs are in clinical trials, with a small number approved to treat specific cancer types.
The next step is to conduct a retrospective study, analysing cancer tissue samples for the biomarkers, in patients who have received Hedgehog inhibitor therapy.
“We could then correlate the biomarkers with how the patient responded to therapy. That would provide some strong evidence as to whether to proceed to a prospective clinical trial, which would actively recruit patients with changes in TP53 and RB1 genes, to receive Hedgehog inhibitor therapy,” Dr Cain said.
What is Hedgehog signalling?
The Hedgehog signalling pathway is a developmental pathway activated in embryonic stem cells, playing a crucial role in babies’ growth in the womb.
After its development role, the pathway is essentially turned off and lies dormant, unless there is a tissue injury in the body, which can switch the pathway back on as part of the healing process. Problems occur when the pathway is activated in healthy tissue, which is associated with the development and progression of cancer.
Dr Vijesh Vaghjiani, a co-first author on the study published in The Journal of Clinical Investigation, said it may be possible to selectively screen for these gene mutations in cancer patients’ tumour tissue (such as those with SCLC) to determine whether personalised treatment with Hedgehog inhibitor therapy would work.
“Taking this discovery from the laboratory to hospitals could be absolutely life-changing for cancer patients,” Dr Vaghjiani said. “It’s why we do what we do.”
- Each year, >2 million people worldwide are diagnosed with lung cancer. About 15 per cent of these are small cell lung cancer and 85 per cent are non-small lung.
- In Australia, it is estimated that 13 258 Australians will be diagnosed with lung cancer and 8641 will die from their disease.
- Brain tumours are the most common solid tumours in children and the leading cause of cancer-related death.
- In Australia, ~100 children are diagnosed with brain or spinal cord tumours every year.
Silver linings in the COVID-19 cloud
Dr Cain says: COVID-19 has definitely restricted our research activities. During the first lockdown, almost everything stopped. Our return to work since then has been in a limited capacity, for wet lab work only, and this largely continued through the second lockdown. We’re still very productive thanks to the efforts of my brilliant staff and students.
Since I don’t spend as much time at the lab bench as I used to, I am exclusively working from home while my staff and students progress essential experiments. All my meetings are conducted virtually on Zoom. Despite this, I am busy writing grants, papers, analysing data and planning experiments with my lab members.
My wife is a midwife at Monash Health, so her work continued while I stayed at home with the kids (Grade 6 and Grade 4), supporting their schooling and cooking meals.
There are many silver linings to this unusual year. This period has enabled me to really think about our research, come up with important ideas, plan exciting experiments and write papers. But equally importantly, it allowed me to spend more time with my family – eat lunch with them, go on walks and bike rides, help with schoolwork – all of which I don’t normally get to do.
Victorian Cancer Agency, Cancer Council of New South Wales, Children’s Cancer Foundation, Bailey’s Day, Australian Government Research Training Program, Monash University Postgraduate Publication Award, Science and Industry Endowment Fund STEM+ Business Fellowship in partnership with Mayne Pharma, Petre Foundation, National Health and Medical Research Council of Australia and Victorian Government’s Operational Infrastructure Support Program.
PreviousFinding the right balance