The Research Explained
90% of the death in women with breast cancer is due to metastatic disease. That is the spread of the breast cancer from the primary site to the other organs. Within that primary tumour there are these special cells known as the cancer stem cells and what happens is these cancer stem cells are completely resistant to the chemo therapy that's done to treat it. Therefore, what happens is the primary tumour shrinks but the cancer stem cells stay alive and dormant. These cancer stem cells then spread across the body and reseed and form new tumours. What we've done in my lab is we really specialise in cutting edge molecular technologies. What we've been able to do is literally peel apart the cancer stem cells so we can go right into where the DNA, the core, the brains of the cancer stem cells are. We've managed to identify key proteins that cause the cancer stem cells to tick and because we've identified the key proteins then over the years we've developed novel drugs that actually completely block the cancer stem cells. Therefore, we are developing a new treatment for metastatic disease that doesn't currently exist.
Our research focuses on the treatment and prevention of metastatic cancer.
What is metastasis?
Metastasis, or metastatic disease, is the spread of cancer from one part of the body to another organ or part of the body. Metastasis is associated with over 90% of cancer deaths.
Why does metastasis occur?
Current cancer treatments target the cancer tumour mass, however they have no impact on cancer stem cells. Even after successful cancer treatment, cancer stem cells remain dormant. Metastatic disease occurs when the cancer stem cells reactivate, enter the blood stream and travel to other parts of the body, leading to secondary cancers. These secondary cancers are usually more aggressive and often occur in areas of the body where treatment options are limited or not available. Too often death follows within a short time frame.
How we plan to stop metastatic cancer?
Researchers at the University of Canberra are fighting metastatic cancer on two fronts.
Metastatic cancer blood test
Our research team has developed a blood test that detects cancer stem cells in the blood stream — a sign that cancer has metastasised. Further development of the blood test to the point that it is ready for use in the clinical setting is expected to produce four key benefits for cancer patients.
- Early intervention when cancer metastasises
Early treatment response is critical for stopping the spread of metastatic cancer.
Our blood test can detect 1 cancer stem cell (CSC) in 7.5ml of blood providing the earliest possible indication that the disease has progressed to the metastatic stage. Currently, metastatic progression of the disease is diagnosed through invasive tissue biopsy and can only be diagnosed well after the progression of the disease has occurred.
Once available to patients the test will allow treatment intervention significantly earlier, allowing more time for treatment before the cancer progresses.
- Guiding treatment decisions for more effective outcomes
Once metastatic cancer is detected our researchers are able to analyse the cancer stem cell biomarkers and predict how the cancer will respond to treatment.
Often oncologists have a range of treatment options available to them. Each treatment option will work for a percentage of patients but an oncologist has no way of knowing which treatment will be most effective for an individual patient. This can lead to multiple treatments being required before a successful outcome is achieved. Patients have to endure the side effects of multiple treatments, have reduced quality of life and lose time. If their cancer is aggressive it may be time they simply do not have.
By predicting which treatment option will be effective, patients will be more likely to receive the most effective treatment as their first treatment.
- Adapting treatment to changes in the cancer
When patients are initially diagnosed with breast cancer a tissue biopsy assesses the hormone status of the cancer. The hormone status influences how the cancer grows and subsequently the treatment options available to the patient. Breast cancer can be HER2-positive or HER2-negative. A patient with HER2-positive breast cancer can only receive HER2-positive treatments.
However, a patient’s HER2 status can change thereby changing the treatment options available to a patient.
Our blood test can determine the HER2 status of breast cancer without the need for a tissue biopsy. This will allow for ongoing monitoring over the progression of the disease. For example, if the HER2 status of a HER-negative patient changes to HER2-positive, their treatment can quickly be altered to a HER2-positive treatment option.
The blood test therefore has the potential reduce the number of patients undergoing ineffective treatment.
- Predicting response to immunotherapy
Immunotherapy is a promising growth area for cancer treatment. Immunotherapy works by strengthening the body’s defence mechanism so that the body can attack the cancer. Immunotherapy is emerging as a preferable form of cancer treatment as side effects are often less severe and immunotherapy may be more successful in preventing cancer recurrence.
Currently immunotherapy is successful in 15 – 40% of patients, depending on the type of cancer. The lower likelihood of success often causes oncologists to employ an immunotherapy treatment only after other treatments have failed. Early research suggests our blood test can predict when immunotherapy is the preferable option for a patient. This will allow immunotherapy to be employed more often for those patients it is most likely to be successful for.
Novel treatment approach
The second branch of our research focuses on the development of novel treatments. Our researchers have identified a pipeline of novel drugs that have the potential to prevent metastatic cancer by targeting cancer stem cells. Most developed amongst these is a novel treatment that blocks stem cell proteins in breast cancer.
Cancer stem cells have the same features as normal cancer cells, however they are resistant to all current standard care drugs, chemotherapy, and radiation.
Our research team is the first team worldwide to discover two nuclear proteins that are critical for the identification of breast cancer stem cells.
Following this discovery the team identified a drug combination that block the proteins. When used in combination with existing chemotherapy drugs the resulting therapy attacks both the cancer cells, and cancer stem cells.
Below you can see how the treatment compares to other treatment methods in pre-human trials conducted to date.
The orange line against the Chemo + CSC drug combination is flat because no tumour remains.
The team envisage that the treatment will be co-administered with conventional therapies and used as a Standard of Care, initially for breast cancer.
Research to date suggests this approach will result in:
- a lower dose of chemotherapy drugs needing to be used;
- reduced treatment side effects due to lower dosages;
- minimal chance of metastatic disease; and
- no more cancer in the original area.
The hope is that this same research strategy can also be applied to develop treatments that combat other aggressive cancers where limited treatment options exist including ovarian, pancreatic and prostate cancer.