Tracking ovarian cancers’ evolution to change approaches to treatment Posted on June 3, 2015March 14, 2018 by Carly du Toit We often think of evolution as a positive thing, associating it with progress, growth and development. But because evolution exists in all living things, including cancer cells, it also presents one of the greatest challenges for researchers as they seek out new ways to outsmart an ever moving target. But thanks to the team of world-leading researchers at the ACRF funded Peter MacCallum Cancer Centre at least four evolutionary processes have now been identified that enable ovarian cancer cells to resist chemotherapy treatments. In collaboration with two other key ACRF-funded research institutes, University of Queensland’s Institute of Molecular Biosciences and Westmead’s Millennium Institute, the research team used whole genome sequencing to analyse tumour DNA samples from 91 patients with high-grade serous ovarian cancer. Their new insights into how these cells genetically change to become resilient will allow researchers to investigate more effective treatments – treatments that are tailored to break through each defensive barrier. The defence mechanisms identified in these cancer cells included everything from “hijacking” genetic switches that enable them to pump chemotherapy drugs out of their way to reshaping and accumulating “scar tissue” which appears to block the chemotherapy drugs. ‘In this research we saw stark reminders of how evolution presents us with incredible challenges – to fight an insidious enemy, you need to understand them, and we’ve made a great leap forward thanks to a truly international collaborative effort ,’ says Peter Mac researcher Professor David Bowtell. Before this clinicians would watch as initially effective treatment became ineffective and cancer cells made an aggressive comeback in their patients. For decades they had little information to guide them when selecting treatment for women whose cancer has returned. ‘The research is a turning-point in the global fight against ovarian cancer it offers great hope to patients world-wide,’ says Professor Bowtell. To date this has been the largest complete DNA analysis of ovarian cancer in the world and it would not have been possible without the outstanding support of ACRF donors. This information was originally published by the Peter MacCallum Cancer Foundation.
Possible cause of world’s most common childhood cancer, discovered Posted on February 19, 2015February 25, 2018 by Carly du Toit Researchers from the Peter MacCallum Cancer Centre have discovered a possible cause of medulloblastoma, one of the world’s most common childhood cancers. Cancer scientists have found mature cells in the brain can revert to basic stem cells and initiate cancer – a process previously thought not to be possible. Trials undertaken in the fruit fly, which shares around 70 per cent common cancer genes with humans, found mature cells, in the absence of a key gene, revert into rapidly dividing stem cells that can cause brain tumours. Dr Louise Cheng, Head of the Stem Cell Growth Regulation Laboratory at Peter Mac and lead author on the study, said, ‘It was thought that, once matured, brain cells or neurons could not go backwards and become stem cells again — but we found this process is in fact reversible. “In our fruit fly model, we found that once a gene called Nerfin-1, which keeps neurons locked in a mature, non-dividing state, is lost, the neurons revert to an out-of-control stem cell state, rapidly initiating cancer and quickly becoming brain tumours.” These findings are significant as medulloblastoma patients often have a faulty version of the human equivalent of this Nerfin-1 gene, called INSM1. “INSM1 is frequently mutated in people with medulloblastoma and we believe preserving the protective role of INSM1 could prevent the reversion of mature neurons into stem cells, and stop cancer initiation in the brain,” said Dr Cheng. “This is particularly important in the current treatment context where chemotherapy is used to target rapidly dividing cells, but does not kill non-dividing, mature cells, which we now know can be a cause of medulloblastoma, potentially explaining why chemotherapy is not always successful in treating brain cancers in the long term.” This discovery that non-dividing cells may also cause cancer now opens the door for cancer scientists to develop of new targeted therapies and drugs with the potential to block this reversion of non-dividing cells and eliminate cancer-causing stem cell populations altogether. This information was originally published on the Peter MacCallum website and can be found here.
‘Liquid’ cancer test to replace invasive biopsies Posted on September 5, 2014February 25, 2018 by Carly du Toit A ‘liquid biopsy’ developed by Melbourne researchers has the potential to determine whether malignant tumours are shrinking, faster and more accurately than ever before. This simple new test would replace invasive tissue biopsies by analysing cancer tumour DNA in the blood. Clinician researcher Dr Sarah-Jane Dawson from ACRF-funded research institute Peter MacCallum Cancer Centre said looking for this circulating tumour DNA in blood had been like ‘looking for a needle in a haystack’. However new-generation genetic sequencing allows a complete snapshot of the cancer to be captured as it evolves. “As the cancer cells turn over they release their DNA into the bloodstream. While we’ve known this for some time, it’s only been recently with advances in genomic technologies that we now have sensitive techniques that allow us to very precisely identify this small fraction of tumour DNA in the blood.” “We think this is a really exciting development and it does hold a lot of promise for making a big difference to the management of cancer patients.” Dr Dawson said. A clinical trial testing the liquid biopsy in Victorian breast cancer patients is due to begin next year. Dr Dawson said in an ideal world, regular biopsies would be taken during someone’s treatment. But often that’s not feasible, and it’s invasive. “By repeating these blood tests regularly, they may give us a very accurate understanding of whether someone is responding to their treatment or not — which is very important for a woman to understand.” “She doesn’t want to be on a treatment that’s not working, or be exposed unnecessarily to side-effects, when she could be switched to a therapy that could be more effective,” Dr Dawson said.[/vc_column_text][/vc_column][/vc_row]
Unravelling ovarian cancer reveals potential new treatment Posted on November 18, 2013February 25, 2018 by Carly du Toit Researchers have taken another step towards understanding ovarian cancer, and in treating one of the most lethal forms of this elusive disease. The findings by researchers from Melbourne’s Peter MacCallum Cancer Centre build on the understanding that some ovarian cancers are driven by the deactivation of the BRCA 1 gene, especially those with high-grade carcinomas. ‘We now know ovarian cancer is a very diverse disease, analogous to a Russian babushka doll,” said Professor Bowtell, senior author of the study, which was published this week in Proceedings of the National Academy of Sciences. “It looks like one doll until you take it apart and find layer after layer — but we’re confident when we have finally separated this cancer into all its molecular groups, we will have a much better chance of improving survival for all women.” Continue reading “Unravelling ovarian cancer reveals potential new treatment”
