Commentary: When fighting cancer there's a science in using the science, Professor David Roder
Research spotlight: Advances in therapeutics, Professor Shudong Wang
Five minutes with: Professor Doug Brooks
Research in action: Helping rural cancer survivors, Associate Professor Jim Dollman
When fighting cancer there’s a science in using the science
By Professor David Roder
A Professor in Cancer Epidemiology and Population Health at UniSA, David Roder AM is involved in a wide range of research, advisory committees and community activities aimed at preventing cancer and ensuring treatment reaches those needing it.
It’s often quoted that between one in three and one in two people will get some form of cancer in their lifetime; sobering statistics that have understandably helped drive an unprecedented level of funding and research into cancer. Hardly a week goes by without an announcement of a breakthrough or a new centre or initiative aimed at reducing the impact of cancer.
We all love people who have been affected and we’d all like to do more to fight cancer. But there is so much research output that it can be hard for policy makers, health professionals and individuals to track through it all and determine what to take on board, and what is not actually relevant to their situation.
As a cancer epidemiologist it is my job to work with clinician scientists and other researchers in putting aside spin, politics and emotion and making an objective evaluation of what – out of all the different research evidence on screening services, treatments and preventative practices – will make the best use of health funds for most people.
There's a science in how to use the science. Every year I work with colleagues and community representatives in going through extensive numbers of research papers and thousands of pieces of data to evaluate what works best and what will deliver the best outcomes from cancer screening, treatment and prevention. And if there is one insight I've gained through all of this analysis that is worth emphasising it is this: the big issue in cancer isn't so much the breakthroughs, it's the unrealised opportunities.
I see a huge investment in research but still a large gap in speed of transfer of research evidence into improved services. There's not a lack of scientific evidence in these regards, rather it's that the evidence isn't being used as quickly and as well as it could be to improve health outcomes.
This is an issue not just in Australia but world-wide, and part of the problem is that researchers are rewarded for getting their work published in journals but not so much for transferring research outcomes to service delivery. Look at a country like the United States, where there is some of the very best research in the world but the US is still a way down the ladder in terms of population health outcomes.
Also of concern are the challenges presented in penny-pinching environments; there’s a growing gap between what we know and what we can actually do. While investment in cancer research is at an all-time high, funding for improved services using this research evidence can be hard to come by and there’s a real risk that even the basic but essential things such as keeping complete and accurate records will fall by the wayside.
So these are some of the problems, but what can we do to overcome them? Quite a lot, actually. It’s about getting government bodies, health agencies and NGOs to work together to look at what’s being done and cooperate to make it better.
It's not enough to conduct research and hope that people have read research reports. We need very concerted efforts to apply the research evidence and determine how we can get the best out of the available money that we have in a way that doesn’t leave sectors of the community behind.
An example of one initiative helping to improve service delivery is a project to develop an advanced data system for Aboriginal people with cancer in South Australia. In partnership with an Aboriginal-driven advisory group and colleagues in the Aboriginal Health Council of South Australia, Cancer Council South Australia and the South Australian Health and Medical Research Institute, we're working to improve the quality of evidence on effects of cancer in Aboriginal populations – looking not just at what types of cancer Aboriginal people have and survival rates, but how well their cancers are being managed and how that compares with non-Aboriginal people's experiences and outcomes.
It may end up in papers that get published in journals, but more importantly it is about improving people’s lives and giving Aboriginal people the evidence they need to advocate effectively for appropriate services.
Another vital project we’re conducting with Cancer Council South Australia, the SA Health and Medical Research Council and SA Health is supporting the use of clinical registries in teaching hospitals in South Australia; these registries are important sources of information and they tell us how effective services actually are. There is a very real risk in a difficult economic climate that these registries will fall over and records won’t be kept for improving health outcomes.
Evaluating cancer screening practices is another key priority; it’s important to find a balance between detecting cancer as early as possible on the one hand and yet not providing treatment of limited or no benefit and wasting resources that would be better spent and save more lives targeting high-risk groups.
It’s not smart to use scarce resources to screen everybody, including people at very low risk, if at the same time there are high-risk groups that miss out. One of our recent projects involved working with a researcher on attachment from Germany, Dr Annika Steffen, in the statistical modelling of risk of colorectal cancer to determine how to screen as few people at “low risk” as possible and at the same time miss as few cancers as possible, while focusing on people at high risk.
I’m sometimes asked what can the individual do to minimize their chances of getting cancer. From my perspective there’s only so much one person can do. While it’s clear that lifestyle can and does affect your chances of being diagnosed with many forms of cancer, it’s also true that fighting cancer needs to be a whole-of-society priority and individually it’s pretty difficult to achieve anything on the scale that’s required.
If we really want to have an impact upon outcomes for cancer patients, much of it comes down to better-targeted services, clearer communication of the evidence available, and empowering communities and those who are at a high-risk to take action.
Experiencing cancer is something none of us wants, but by working together there is so much that we can do to put research into practice and ensure that individuals and populations have a fighting chance.
For more information on the Sansom Institute's research activities please visit our webpage
Advances in therapeutics
New medicines to treat cancers while avoiding the toxic side effects of chemotherapy are a step closer to reality thanks to the pioneering efforts of Sansom Institute scientists.
Led by Professor Shudong Wang, Head of the Sansom Institute’s Centre of Excellence in Drug Discovery and Development, a multidisciplinary team has identified several anti-cancer drug candidates which have been shown to effectively target cancer cells with minimal toxicity to normal cells.
One of the most developed pre-clinical drug candidates named CDKI-73 has demonstrated potent anticancer activity against wide spectra of tumour cell lines. The compound is particularly efficacious against chronic lymphocytic leukaemia, the most common type of leukaemia, but also shows low toxicity to normal B-cells and T-cells. CDKI-73 is an orally deliverable drug, and is currently in the late stage of pre-clinical development; the aim is to take it into clinical trials in leukaemia patients.
CDKI-73 targets cyclin-dependent kinases (CDKs), a group of enzymes that regulate cell cycle, and transcription, and that promote cancer cell proliferation and survival.
Targeting CDKs has been seen as one of the most promising anti-cancer strategies since the enzymes were discovered by Paul Nurse and Tim Hunt, who went on to win the 2001 Nobel Prize for their work.
During the last few years Professor Wang and her team have been at the forefront of the race to target CDKs after identifying a particular enzyme, CDK9, that is involved not only in cancer, but also HIV and cardiac hypertrophy.
"We're focussed more specifically on cancer, and have designed a series of CDK9 inhibitors that have been shown to be effective against leukaemia and solid tumours without causing the significant damage to normal cells that is usually seen with chemotherapeutic drugs," Professor Wang explains.
"We hold US, UK and China patents and are working with an industry partner aiming to take CDKI-73 to clinical trials."
Another class of promising drug candidates being developed target the mitotic kinases which are critically involved in the regulation of cell division. Cancer is essentially a disease of mitosis – cancer cells proliferate or divide at an uncontrolled rate. Professor Wang has identified several orally active and highly potent mitotic inhibitor compounds that can slow the progression of pancreatic, ovarian, and colon cancer cells.
"Pancreatic cancer is one of the most deadly cancers, so discovering a compound that can treat it is an exciting development," Professor Wang says.
With at least three anticancer drug candidates in the development pipeline, Professor Wang puts much of the success down to her multidisciplinary focus.
"I have a multi-disciplinary team of scientists with expertise in computational drug design, medicinal chemistry, cell biology, and pharmacology. We are able to carry out all the discovery and pre-clinical studies in-house in a coherent manner, which is relatively rare in an academic institute. This has enabled us to rapidly advance a drug program from discovery towards clinic," she says.
The main barrier to progress these drug programs, says Professor Wang, is funding, with the multimillion-dollar price tag stopping many promising drug candidates from reaching their clinical potential.
"It sounds like a lot of money but it’s a worthwhile investment in new cancer therapeutics that can save millions of lives."
Five minutes with...
Professor Doug Brooks
The leader of the Sansom Institute’s Cell Biology of Diseases Research Group, Professor Doug Brooks is combining his knowledge of cancer biomarkers and the endocytic network to develop new, more effective tests for prostate cancer.
You spent much of your career working on Lysosomal Storage Disorders and you are now developing a new screening test for prostate cancer. What prompted the shift?
I actually started my research career in cancer – I did my PhD in cancer biology, and went on to examine cancer biomarkers for B-cell leukaemia as a post-doc; that work resulted in a commercialisation that is still helping to diagnose cancer and fund research. I changed fields to work at the Women’s and Children’s Hospital on Lysosomal Storage Disorders, a group of inherited metabolic disorders that can cause everything from developmental delay to mental retardation. These diseases are rare but devastating and for 25 years I worked on all aspects of the disease, from developing diagnostic tests to better treatment strategies.
A few years ago I was at the point of deciding whether to continue in the area I’d specialised in or to adapt it to another field. I’d been thinking about lysosome markers a lot – lysosomes being proteins that have been studied in cancer biology and diagnosis – and I started to wonder if the mechanisms of endosomes and lysosomes that I’d been looking at in my work for so long could have direct relevance to cancer. It made sense because they’re involved in cell division and they’re the main secretory system that operates between the inside and the outside of the cell.
I chose to focus on prostate cancer because as well as it being very common, a couple of former colleagues – Lisa Butler and Wayne Tilley – were involved in the field, and there was already that trust there. So we got together and looked at the biology and found out that endosomes are significantly altered in prostate cancer – this was previously unknown and opened up the door to developing a new, more effective screening test for prostate cancer.
We've heard a lot lately about prostate cancer being over-diagnosed, and men being subjected to needless surgery with unpleasant side-effects…
Our test is shaping up to be a lot more accurate than others. The PSA (prostate specific antigen) currently used to test for prostate cancer is very sensitive on the one hand but only picks up abnormalities in certain patients on the other, so there are a lot of false positives and a lot of false negatives. People can show a high PSA reading just from spending a lot of time cycling or from getting an unrelated infection, so the search is certainly on for better tests.
We've carefully studied cells that have been looked at in prostate cancer and discovered some of the cell markers being used in testing are not suitable. We're able to distinguish between normal control cell lines and malignant cell lines, and our markers are a lot more reproducible than current markers, which makes us think we’re onto something that can reduce the problem of over-diagnosis.
It's exciting how far we've come in four years, from an idea to being on the cusp of translation into a clinical outcome. Initially we kept it all very quiet and were funded on a shoestring, now we have a provisional patent and are developing assays involving a PhD scholar, funded by ITEK, the South Australian Health and Medical Research Institute and UniSA’s Division of Health Sciences.
You're also looking at breast cancer…
Yes, we’re doing a similar sort of study on breast cancer, supported by a new concept grant from the National Breast Cancer Foundation. We are feeling our way in terms of cell biology to see if it's the same as prostate cancer – it's early days but I don’t think it is the same.
Your job brings you from the lab to the lecture theatre and over the course of your career you've mentored many students; what do you enjoy most about your job?
As a researcher, the translational outcomes and being able to have an impact upon people's lives is extremely satisfying; it's the ultimate outcome for any medical researcher.
Teaching and lecturing are very rewarding as well. Every student is great in their own way – they all give you a different perspective on how to deal with people and with research problems; some of them even drive your research and that can be quite threatening!
One example is Barry Lewis – now head of Clinical Biochemistry at Pathwest at the Princess Margaret Hospital in Perth – who taught me more about writing than I taught him about research. I kept telling him to write his thesis and he kept telling me he was planning. When he showed me his plan he had the start and end of each chapter with dot points in-between. He spent six weeks on the plan but he wrote the thesis in two weeks, and it hardly needed a single correction!
Looking to the future, what do you see as the ultimate goal or breakthrough in the cell biology of cancer?
We'd like to get a cancer therapeutic – ultimately, a cure – and that's where we're intending to go with our prostate and breast cancer work. The most practical thing that we can do at the moment is to understand the cell biology so we can improve screening assays; then we want to build on those findings so there’s a clearer vision of where we can go. We're in an ideal position here at the Sansom Institute, working alongside colleagues like Professor Shudong Wang and others who are making real headway in the fight against cancer.
Research in action
Helping rural cancer survivors
Cancer survivors from around rural South Australia have been the first to trial an innovative new lifestyle support program developed by researchers from the Sansom Institute for Health Research.
The 12-week Step Towards Diet and Exercise (STRIDE) program combines an online tool with individual support to help improve physical activity and dietary behaviours in rural cancer survivors, a group that tends to have poorer outcomes compared with their metropolitan counterparts, according to research by co-leader Associate Professor Jim Dollman.
"Cancer survival rates are lower in the country and a big factor driving the disparity is poor access to support services due to isolation – this study was designed to address that through a computer-delivered intervention," Associate Professor Dollman says.
While a growing body of research has linked a lack of exercise and physical activity to higher rates of some types of cancer, the emphasis with this program is to support cancer survivors to look after themselves at a time when other services tend to drop off.
"The evidence is very strong for a range of cancer types that encouraging an exercise habit and physical activity improves quality of life, helps in weight management and in-turn lowers the risk of chronic diseases such as diabetes," Associate Professor Dollman says.
"Most survivors are aware of this, but unfortunately once they’ve completed treatment they’re often left alone; it can be a tough time for them because in their minds they’re still fighting the cancer."
In the trial of the program, participants from Port Pirie, the Riverland, the Copper Coast and Adelaide were provided with pedometers and IT support and encouraged to input their daily activity levels into an online tool.
Sansom Institute based researchers from the Exercise for Health and Human Performance group reviewed each case and provided immediate support to help participants set worthwhile but realistic activity goals.
Research co-leader Associate Professor Gaynor Parfitt, says that participants are encouraged to reflect on how they feel each day, and to integrate as much incidental activity into their lives as possible.
"There’s an acceptance that they will take days off, or do less activity, if they’re not feeling well or if they have to travel long distances for treatment," she says.
"If you can take into account how they’re feeling and give them a goal that’s more achievable, they’re more likely to do it and stay motivated."
"The main thing is we don’t want them to give up, we encourage them to think of every day as a new day."
The program uses knowledge gained from recent research by the group into exercise intensity and self-regulation that shows people are much more likely to enjoy exercise and maintain physical activity if they are taught control processes and self-regulation techniques.
As well as the physical benefits, the program has helped participants to connect socially and access local services and forums via the website, thanks to the integrated IT support.
"Many of the participants were older people, and some didn’t start off very confident in using a computer," Associate Professor Dollman says, "but once they became more comfortable with the technology they started to enjoy using it for other purposes, like staying in touch with family and friends."
"As the internet becomes more widely used it’s become a more useful tool in health care, and the possibilities with integrating consultations via Skype is just one of the extras that could be added to the program."
"In future we can envisage the program being utilised by local health care services and councils, perhaps with IT support provided via the local library."
The group is now adapting the model to be used in cardiac rehabilitation.
Funded by a Supporting People with Cancer grant from Cancer Australia, the STRIDE program is a joint initiative with Country Health SA, Community Centres SA, and the Riverland and Yorke and Lower North Health Services.
For more information on the Sansom Institute's research activities please visit our webpage