Overview of New Therapies for Ovarian Cancer & Prostate Cancer
Associate Professor Jonathan Harris
Associate Professor Jonathan Harris is a biochemistry researcher at Queensland University of Technology in Brisbane. His specialty is drug design. He tailors new molecules to tackle targets on cancer cells.
There are currently 20,000 men living with prostate cancer, and every year 1400 women are diagnosed with ovarian cancer. There are some similarities between these two diseases, Associate Professor Harris explained. They're both hormone dependent and both can impact on a patient's fertility. Both diseases can have good outcomes when detected early, but because they don't have many symptoms in the early stages, late diagnosis is associated with poor prognosis. This is why it is crucial to develop simple, non-invasive diagnostics that could detect cancer well before symptoms appear.
The differences between prostate cancer and ovarian cancer relate in part to the way they are treated. Side-effect profiles of the different therapies can vary, moreover the surgical procedures can differ due to the locations of those organs and the complexity of the surrounding tissues. Associate Professor Harris also noted that there are a wide variety of treatments available for both diseases but individuals will respond to these treatments differently.
Older treatment methods are fairly blunt, he said. A tumour cell was defined by the idea that they divide rapidly and based on that they found ways to destroy them. But this approach is associated with a lot of DNA damage and toxicity and we are now after smarter, more targeted approaches. "There is a huge raft of changes happening in both ovarian and prostate cancer," he announced. These stem from changes in the way research is carried out. This comes from an increased level of interaction between clinicians and researchers.
There has also been a growing appreciation of how the immune system affects cancer and this has led to a focus on the development of a way to prompt the immune system to attack cancer cells. Artificial antibodies are one such way to do this. The antibodies are tailored so that they seek out cancer cells. Moreover, researchers are finding ways to attach toxins to those antibodies so that the cancer cell receives a toxic hit. It is now possible to also tag imaging molecules to the antibodies so that they make it easier for researchers to visualise the tumour in the body, including previously undetectable micro-tumours.
He added that the ability to rapidly and cheaply read a patient's genome is making a big difference in research. The first genome took 10 years and nearly 3 billion US dollars to read. We can now do this in the space days and for less than a few thousand dollars, and these will drop further in coming years. This provides a lot of information on how to tackle cancer, because there are genes that drive cancer and there are genes that determine how a patient will react to treatment. This will guide the development of new, smarter ways to stop cancer as well as identify important risk factors.
Associate Professor Harris highlighted several therapies that are new to the clinic. Advanced prostate cancer can become resistant to hormone therapy. Abiraterone (Zytiga) prevents those cells from synthesising the testosterone that would drive tumour growth. Denosumab is another treatment which helps protect bone in advanced prostate cancer, by blocking the activity of bone destroying cells so that patients don't lose bone density. Olaparib (AZD 2281) is a new treatment for late stage ovarian cancer. It blocks DNA repair in tumour cells, which increases the effectiveness of chemotherapies that damage DNA, enabling the patient to receive a lower, less toxic dose. Trials in prostate cancer and ovarian cancer have been conducted. Bevacizumab (Avastin) is a new antibody treatment for advanced ovarian cancer. It blocks the growth signals required for the formation of capillaries around the tumour, thereby starving it of nutrients. Bevacizumab has also been used successfully in colon cancer.
There is also a lot of basic laboratory research underway with promising results, explained Associate Professor Harris. It is known that certain enzymes called proteases can promote tumour spreading. A molecule derived from sunflowers appears to be able to block this activity. Furthermore, it is now known that cancer stem cells lead to tumour regrowth. Cancer stem cells are a population of cells that can develop into a tumour, but they are difficult to treat because most current treatments target cells that rapidly divide, whereas these stem cells don't. They're often the source of cancer recurrence, explained Associate Professor Harris. But he is optimistic. "We are getting a better at understanding the nature of these stem cells so that we target them."
Click here to see Jonathan's presentation slides
New Vaccines for Prostate Cancer
Associate Professor Kristen Radford
Associate Professor Kristen Radford is an immunologist at Mater Research Institute which is based at the Translational Research Institute in Brisbane. She has been working in the field for twenty years and she is looking at how the immune response identifies and fights cancer cells. She identifies her work as basic science, because she is trying to find out the fundamentals of how these mechanisms work.
Her research is contributing to the development of promising new treatments. Associate Professor Radford explained that over the past twenty to thirty years scientists have learned that the immune system can recognise and fight cancer and there has been a lot of research chipping away at the puzzle. There are now three main approaches of cancer immunotherapy:
(1) By turning off the breaks in the immune system, by targeting known checkpoints that prevent an immune reaction;
(2) by removing a patient's killer T-cells, sensitise them so that they seek out cancer cells, then return them to the patient's system; and
(3) by developing vaccines.
Associate Professor Radford's work focuses on the vaccine approach. Dendritic cells are master regulators of immune responses, she explained. They initiate immune responses against pathogens and cancers. They also promote immune tolerance. Dendritic Cell immunotherapy involves removing a patient's white blood cells, then isolating the dendritic cells. The researchers expose the dendritic cells to the cancer in order to make them react. They then return the dendritic cells to the patient's body. Once inside, the dendritic cells talk to the other immune cells that then seek out and kill the cancer wherever it exists in the body. As a proof of concept they have done a phase one trial looking at safety and dosing in patients. While this showed the technique worked in principle, it is not an ideal treatment itself because removing patient's cells, handling them and returning them to the patient is a costly and time-consuming method and can be risky. That's why they are looking at a vaccine approach that will have the same effect. They have discovered that there is not just one type of dendritic cell, but many, and that there is one type in particular that fights cancer cells. They can now tailor a vaccine that only targets that type of dendritic cell. Essentially, they've developed an antibody that targets that cell type and they've attached molecules that help the dendritic cell recognise certain types of cancer. This approach is expected to be non-toxic, safer and more cost effective than the cell-removing-replacing approach.
"This approach is a revolution," said Associate Professor Radford. "It's not a magic bullet - it needs to be used in combination with other treatments, but it has great promise."
Click here to see Kristen's presentation slides
Personalised treatment for ovarian cancer
Professor Lewis Perrin
Professor Perrin is a Gyne-oncologist, specialising in surgical cancer research. He spoke to the audience about epithelial Ovarian Cancer, its prevalence, its effects and its treatments. Ovarian cancer is the fifth commonest cause of female cancer death and in Queensland there are about 260 new cases diagnosed each year.
One of the key differences about ovarian cancer compared to many other cancers is that 75% of patients present with advanced disease, primarily because early symptoms are either not present or are vague. Another difference is the response to surgical treatment. Professor Perrin explained that in many extensive cancers, surgery doesn't have a big effect, but that removal of an ovarian cancer tumour mass can have a big effect particularly on the patient's quality of life. At this point, however, the disease returns within two to five years after the surgery so there is a desperate need for more effective treatments and advanced screening. He noted that one type of surgery doesn't fit all, and the same goes for chemotherapy. There is a lot of work toward personalised treatment and screening in ovarian cancer, and in this, he sees a cause for hope.
Ovarian cancer is not one disease but is made up of several different subtypes of cancer. The more researchers learn, the more they are able to identify different genetic profiles that make particular subtypes of ovarian cancer prone to specific chemotherapies. It enables clinicians to choose the best chemotherapy agent for the patient, and to avoid agents that don't work. Curing ovarian cancer is the ideal, but another avenue also being pursued is to find ways to turn ovarian cancer into a chronic disease, where patients are treated for every recurrence, each time forcing the cancer back into remission.
Professor Perrin is involved in the Queensland Centre for Gynaecological Cancer, which is a team of eight gynaecological oncologists delivering cancer care throughout the state. The Centre treats the majority of ovarian cancers in Queensland, and deals with approximately 260 new cases each year. There is a significant improvement in survival if patients come to one of the centres. The QCGC is a multi-disciplinary collaborative cancer research model where each of new cases are presented to a multidisciplinary board made up of doctors, nurses, scientists and mental health professionals. They examine each case to determine optimal treatment. While cure is the aim, quality of life is equally important. They also look at options for clinical trials.
New research efforts are looking into different proteins which enable the cancer to spread throughout the abdominal cavity. Professor Perrin noted that malignant cells are able to survive while floating around in abdominal fluid. Blocking this ability could make big difference to disease progression. Other research is looking at the genome of the patient and comparing it with the genome of the tumour itself in order to identify changes. They are also looking at the genomic profile of the tumour after treatment to check if there have been any changes to the genome which may affect subsequent therapies. Tumour biopsies are required to facilitate this type of research. Studies are being completed exploring how the tumour behaves in mouse models. This can pave the way to the development of new treatments and is an important stepping stone to new clinical trials.
Professor Perrin emphasised several crucial goals for the next five years:
- Ensure all patients have the option to have detailed analysis of their tumour type
- Communicate findings – not only does this inform patients, it helps recruit experts
- Obtain funding for staff recruitment
- Expand funding for project work
- Expand local, national and international collaborations
- Translate research findings into clinical trials
- Further translate findings via links with the pharmaceutical industry
Click here to see Lewis' presentation slides
Does lifestyle influence quality of life and survival following a diagnosis of ovarian cancer?
Professor Penny Webb
Professor Penny Webb is a cancer epidemiologist at the QIMR Berghofer Medical Research Institute, where she heads the gynaecological cancer group.
Professor Webb explained that the primary factors known to influence survival in relation to ovarian cancer are age and the presence of mutations in the BRCA genes. She noted that although the presence of a BRCA mutation can increase the risk of ovarian cancer, patients who possess BRCA mutations tend to have better survival rates than ovarian cancer patients who do not.
Other factors influencing overall survival are the subtype of cancer, the grade and the stage. Chemotherapy and surgery are both important to outcomes, but Professor Webb explained that any two patients with similar ovarian cancers and similar treatment regimes may have very different outcomes. This is where her interest lies. She wants to know if there are things people can do to improve their survival and quality of life. She is interested in diet, vitamin supplements, and body size as well as behaviours such as smoking, drinking alcohol, and exercise.
At this stage there is much that remains to be determined about which lifestyle factors are most influential and very little work has been done in ovarian cancer thus far. However, information based on research on other cancer types may be informative.
Studies across cancer types indicate that physical activity is crucial. The more active you are, the better your outcome. The effect of diet and body size is less clear. In one study a healthier diet was linked with a more beneficial outcome, yet in a second study there was no difference. However when the data were re-examined, the patients with improved outcomes in the first study had also experienced some weight loss. This suggests body size may play a role. Indeed a number of studies have shown that obesity is associated with worse overall survival.
Alcohol intake is another factor influencing cancer. Alcohol is known to increase the risk of getting breast cancer, but little is known about its effect on survival once the cancer is established. Smoking is another lifestyle factor that can negatively affect outcome, with studies showing non-smokers had better survival post-diagnosis. Conversely, vegetable consumption has been shown to improve survival rates.
Professor Webb also highlighted the role some common medications may play in patient outcomes. There is some evidence that aspirin may lower risk of certain cancers and in heart disease trials, aspirin was associated with lower cancer mortality. Statins, which are cholesterol lowering compounds, have been associated with increased survival in prostate and breast cancer. Finally, there is evidence that Metformin, a drug used to control blood sugar in diabetics, may lower risk in some cancers.
Professor Webb and her colleagues have commenced the OPAL (Ovarian cancer Prognosis And Lifestyle) study that is taking a closer look at how survival is influenced by wide variety of factors including ancestry, reproductive history, weigh, height, medical history, insomnia, and lifestyle. They are currently recruiting one thousand cancer patients for this important long-term study.
Click here to see Penny's presentation slides
Psychosocial care for men with prostate cancer
Professor Suzanne Chambers
Professor Chambers is a health psychologist who has worked with cancer patients for more than twenty years. She is particularly interested on how the distress associated with cancer diagnosis and treatment impacts on the wellbeing of patients. She explained that there is a wide profile of negative effects following diagnosis and these can depend in part on the type of treatment a patient may undergo. For example androgen deprivation therapy can lead to bone density loss, whereas radiation can have sexual health effects as well as bowel effects. Professor Chambers explained that factors such as younger age at diagnosis, poor social support and treatment severity can influence how distressed a patient may feel. Moreover, patients may experience peaks of distress over the course of the disease, and patients' partners are also prone to distress.
10 - 25% of men are distressed by a diagnosis of prostate cancer, but the chance of that distress being identified is very low. Furthermore, the psychological care they receive is can vary. Perceptions of masculinity play a role in how men feel about their diagnosis, because masculine values of self-reliance, strength and stoicism can prevent patients from seeking help when needed. Professor Chambers' work focuses on finding ways to help lower distress and to teach coping skills. Physical exercise is a key component to improving quality of life, by improving general health as well as reducing fatigue. With regard to prostate cancer, she is interested in developing accessible models of intervention. In other words, she is researching masculine values in order to find ways to work with prostate cancer patients to identify and manage distress. Professor Chambers and her colleagues have recently published a book called Facing the Tiger, which can be accessed via Prostate Cancer Foundation of Australia.
She and her colleagues have also validated a Distress Thermometer in prostate cancer patients which enables them to better understand the points at which distress arises and peaks, and is also working with an international team of researchers to develop a psychological care model. This model can help service providers assess distress from mild to severe and provide them with clear recommendations for treatment at each level.
Click here to see Suzanne's presentation slides