Hopes of finding an early-warning signal for ovarian cancer have been boosted by a protein discovery at the Hunter Medical Research Institute (HMRI).
A research team from the University of Newcastle and Hunter New England Health, comprising cancer scientists, oncologists, gynaecologists and geneticists, spent three years investigating the earliest lesions involved in the disease with the goal of developing a biomarker test.
As published in the international biology journal Development, they detected elevated levels of ‘Wnt’ proteins being secreted by ovarian lesions.
This signalling, in turn, regulates a stem cell in the fallopian tube that spurs cancer formation. “The lesions are so small they can’t be seen with MRI, ultrasound or a camera until it’s too late. But we now have a good sketch of the thief, which will help us to catch it,” lead researcher Dr Pradeep Tanwar, from the University of Newcastle, says.
“We found out how the lesions formed, and what the switch is.” He believes the discovery could have a significant bearing on survival rates. “The majority of women with ovarian cancer are diagnosed with advanced [Stage 4] disease because the symptoms often echo more common ailments such as stomach bloating and changes in bowel movements,” Dr Tanwar adds.
“It’s difficult for women to pinpoint the exact symptoms and also challenging for GPs to diagnose, as in the majority of patients these symptoms are not from cancer.
“Those diagnosed with Stage 1 ovarian cancer have a 90% survival rate, compared with 44% overall for later stages. At Stage 4, just one in 10 women will survive beyond five years.”
At Stage 1, the lesion can be surgically removed and many patients don’t require chemotherapy if physicians are confident the growth is localised to the ovary or fallopian tube.
Stage 3 and 4 ovarian cancer, despite some patients being cured by surgery and chemotherapy, will relapse in the majority of women and is almost always incurable when it does recur. Additionally, there is a genetic predisposition for women who are BRCA1/2 positive – the same genes implicated in breast cancer.
Those who have BRCA 1 or 2 have a significantly higher risk of developing ovarian cancer over their lifetime than women without these inherited gene faults. “Younger women with a BRCA risk may be reluctant to undergo surgery to remove their ovaries and fallopian tubes as this has implications for child-bearing as well as early menopause,” Dr Tanwar explains.
“If we can track Wnt proteins, doctors can make clinical decisions on ongoing risk and help women make timely decisions about surgical risk reduction.
Our study is now looking at detecting these proteins in fluid and cells collected during a conventional pap smear or in a separate, simple procedure.”
A collaborator from Curtin University in Perth, Professor Arun Dharmarajan, has developed an inhibitor for Wnt proteins that may stop the lesions from developing any further. It is in preclinical modelling as the next phase.
Calvary Mater Newcastle medical oncologist Dr Janine Lombard believes the research is a bright light in an otherwise dim area of early detection. “Despite decades of reaseach we still have no way of effectively screening for this cancer, even in women with BRCA1 or 2 gene faults who have a much higher risk of this cancer than the general population of women,” Dr Lombard says.
“It’s very exciting to see research from Dr Tanwar’s group in the Hunter potentially identifying a new way forward in this important area.”
Samples for the study were sourced from the Hunter Cancer Biobank, along with ovaries and fallopian tubes donated by BRCA 1/2 patients following surgery at the John Hunter Hospital.
Collaborators include Laureate Professor Rodney Scott, Director of Molecular Medicine in the Hunter Area Pathology Service; John Hunter Hospital gynaecologists Dr Pravin Nahar and Dr Ken Jabaack; and Professor Peter Hoffmann from the University of Adelaide.
Dr Tanwar, a Cancer Institute NSW Fellow from the University of Newcastle, and Calvary Mater Newcastle medical oncologist Dr Lombard research in conjunction with HMRI’s Cancer Program. HMRI works in partnership with the University of Newcastle, Hunter New England Health and the community.
UNIVERSITY OF NEWCASTLE