The tumour microenvironment: Identification of novel cancer biomarkers and therapeutic targets
Ovarian cancer is a devastating disease and the leading cause of death from gynaecological cancers, affecting approximately 1 in 90 women in Australia. Over 70% of patients present with advanced disease, and despite improvements in surgery and new developments in chemotherapy, ovarian cancer mortality rates have not changed dramatically over the last decade.
Significant improvement in ovarian cancer survival will require;
- The development of new ovarian cancer biomarkers (biological indicators of disease) for early detection and
- More effective molecularly targeted therapeutics (i.e. drugs that interfere with cancer cell growth and survival).
Our research is focused on greater understanding of the mechanisms of ovarian cancer spread, resistance to chemotherapy and the identification of novel biomarkers for ovarian cancer detection.
What we aim to achieve
The two major challenges in improving ovarian cancer survival outcomes are;
- The identification of cancer markers to improve early diagnosis and
- The discovery of new therapeutic targets (cells and molecules involved in cancer development that can be targeted) for effective treatment of advanced disease and treatment of resistance to chemotherapeutic drugs.
Our work to date has made substantial progress towards both of these goals through targeting the protein annexin (A2). We have shown that annexin A2 is highly expressed in 90% of serous ovarian cancers (the most common subtype) and is actively involved in the process of ovarian cancer metastasis (the spread of cancer cells to other sites in the body).
We expect that our study will provide a strong rationale for targeting annexin A2 in serous ovarian cancer patients. Our findings will provide important groundwork to inform further testing of annexin A2 inhibitors for clinical studies in the future.
Chemoresistant cancer is the major cause for ovarian cancer death and has very limited treatment options. Our recent data demonstrate that the sugar molecule hyaluronan (HA) play an important role in the development of platinum-based chemotherapy resistance. Ongoing studies plan to define the mechanisms involved, and identify key HA-regulated proteins that could be targeted to overcome chemoresistance. Reducing HA production or interactions with other proteins may reverse chemoresistance and promote cancer cell death, ultimately leading to improved survival.
We expect that specific proteins are involved in chemoresistance in ovarian cancer cells. These may also be potentially targeted to reverse chemoresistance in ovarian cancer cells.
We will also determine whether HA and HA-regulated proteins can be used as markers to identify ovarian cancer patients at high risk of developing chemoresistant disease and early recurrence.
Earlier diagnosis of chemoresistance in patients with ovarian cancer would have important treatment implications. It would allow tailoring of therapies to individual patients. It would also prevent unnecessary toxicities in those patients who are chemoresistant and would not benefit from the treatment. Instead, they could be enrolled in clinical trials earlier or treated with other experimental therapeutics to improve survival.
Our research holds promise to result in new methods of early ovarian cancer detection and treatment strategies to improve patient survival.
Our next steps and milestones
Ongoing studies will identify the different roles that the protein annexin A2 plays and will evaluate the effectiveness of a range of strategies to block annexin A2 function. These will be tested in the lab using models of ovarian cancer.
Our research will generate evidence that annexin A2 inhibitors can be used to improve ovarian cancer survival, and will inform further testing of annexin A2 inhibitors in future clinical studies.
What motivates me?
My ultimate aim is to improve survival outcomes for people diagnosed with cancer. Recently, I was touched by cancer in a personal way when my sister was diagnosed with breast cancer. My personal experience has made me even more determined to work as hard as possible to make a difference.
My message to supporters
Cancer Council SA funding has provided essential funds for our research investigating how cancer cells develop and spread in the body. My work has focussed on better understanding the interactions between cancer cells and their environment. We have identified novel ways that ovarian cancer cells use their environment to aid their growth and mobility which enable them to spread to other sites in the body.
We are also investigating whether proteins that are altered by interactions between cancer cells and their surrounding environment can be used as new markers to detect ovarian cancer at an early stage before it spreads to other sites in the body.
Funds from Cancer Council SA are currently being used to investigate potential new drugs to treat ovarian cancer in the future. Better cancer treatments are urgently required particularly for ovarian cancer, which has a poor prognosis. Funds from Cancer Council SA are used directly to fund researchers like myself. My ultimate aim is to improve the survival outcome for people diagnosed with cancer. We are very grateful for all the hard work and dedication from supporters of Cancer Council SA that have helped raise funds for important cancer research in South Australia.