Tackling Silent Killers
By investigating the pathogenesis of female reproductive tract cancers, Professor Pradeep Tanwar aims to develop targeted therapies to improve clinical outcomes.
Professor Pradeep Tanwar and his team are methodically investigating questions surrounding female reproductive tract cancers from several different angles.
An investigator of the Hunter Cancer Research Alliance, the potential massive impact of Pradeep’s work has been recognized by his appointment as an NHMRC Career Development (CDF2) Fellow..
“We work on female reproductive tract cancers,” Pradeep explains.
“We mainly focus on two cancers - ovarian cancer, the most deadly of gynecological cancers in women, and endometrial cancer or cancer of the uterus, which is the most common gynecological cancer in females.”
“What we are interested in is how the cancer develops to start with, and once it has developed, how does it progress to a stage where it spreads to other organs,” he says.
“And when it spreads, how can we control it. So we are interested in both how we can control the development or initiation, and how we can control the spread, of these cancers.”
A needle in a haystack
Pradeep explains that genetics, lifestyle factors, and age, are all risk factors for reproductive tract cancers.
“But having a genetic predisposition does not mean these cancers will develop, so lifestyle factors play a role”, Pradeep explains.
“You will find two thousand factors that are different between a patient that has cancer and a patient who does not have cancer, a patient who has metastasis versus a patient who does not have it.”
“So, what are those differences? What combination of factors result in the actual development of the disease? We are looking for a needle in a haystack. But that might be the key.”
Breakdown in cell communication has been identified as a factor in increased incidence of cancers as has been patient’s age, so this communication process is also being studied.
“Cancer is basically excessive production of cell types,” Pradeep says.
“Every day billions of cells are regenerated in the body, and a number of cells need to die to keep everything in perfect harmony. The signals that keep this system in harmony are sometimes disrupted. We hope to discover a way to correct that disruption.”
With lack of population-wide screening program, symptoms that can mimic other conditions, and diagnostic procedures that are difficult and non-conclusive, cancers of the reproductive tract are notoriously illusive and are most often diagnosed in later stages.
Pradeep’s group use genetically modified animal models, cancer patient-derived xenograft models and primary human tissue samples to define the molecular and cellular events involved in carcinogenesis.
The Hunter Cancer Biobank (HCB) at the Hunter Medical Research Institute (HMRI) collects affected patient tissue, which is then provided to researchers. In this important way, many cancer patients through the Hunter and surrounding areas have contributed to this and other cancer research.
Utilising animal models allows researchers to target early stages of the disease and investigate possible markers that may be identified through existing pathology test processes, ultimately facilitating more timely diagnosis.
Working with these models also allows the team in the lab to bombard tumorous tissue with combinations of off-label medications. Pradeep is hoping to find a medication, already approved and mass produced, or combination of such, that can be repurposed to aid in the fight against these cancers.
Working with a former Harvard colleague, Pradeep has already made a major breakthrough in identifying a protein that can act as a tumour suppressor when treating chemo-resistant ovarian cancer.
He has recently published a paper showing that in animal models and human ovarian cancer cells, progesterone suppresses and oestrogen promotes the growth of cancer cells.
“We were able to find that the initial lesions of ovarian cancers had receptors for oestrogen and progesterone. So if you have too much estrogen, those lesions will develop into cancer.”
As a result of this work, his team including clinicians are exploring the use of hormonal treatments in combination with chemotherapy for reproductive tracts cancers.
“The incidence of cancer in patients is much higher for those who have never used oral contraception than in patients who have used oral contraception,” Pradeep asserts.
“If you take the Pill it suppresses your ovaries and you are less likely to develop ovarian cancer, all reproductive tract cancers.”
“This is vital information for women who may be at high risk due to family history, and women who are postponing pregnancies until later in life.”
The path to here
Pradeep is originally trained in veterinary medicine and animals first ignited his passion for discovering disease prevention strategies.
Frustrated by the amount of animals being put down due to prohibitive treatment costs, Pradeep reasoned that facilitating the maintenance of animal health and worth removed the necessity for large treatment costs, long recovery periods or euthanasia.
“One of the things I also learnt as a veterinarian is that the underlying principle of animal domestication seems to be production. Without reproduction, there is no production. If a cow is not breeding, a farmer is going to get rid of her.”
This principle lead Pradeep to become invested in the study of reproductive systems. A PhD at the University of New England furthered his study of this system in women. A post-doctoral stint at Harvard followed.
“At Harvard, you are embedded in a hospital, so you have oncologists, surgeons, gynecologists, obstetricians, and researchers, all having lunch at the same time,” Pradeep recalls.
“They were discussing their patients and we were discussing our research. I became more and more interested in ovarian and uterine cancers, and learnt a great deal.”
These experiences have resulted in Pradeep establishing a lab environment which comprises of both systemic and specialized approaches in addressing a research problem. Pradeep’s lab also addresses fundamental questions regarding the normal functioning of the female reproductive tract, such as the cellular dynamics. Often answers to these questions helps in understanding what is going wrong with the system leading to disease development.
When reflecting on the many challenges to the diagnosis and treatment of female reproductive cancers, Pradeep cites the increased incidence of obesity amongst women as a major hurdle.
Pradeep and his team have spent four years investigating the role of fat cells in the growth of cancer cells. By providing accessible fuel, fat deposits in the body can accelerate and feed cancers. This process is particularly relevant to ovarian cancer, which metastasizes first to the omentum (a fatty tissue).
“These cancer cells have free food and a free supply of energy,” Pradeep explains.
“But if we can find ways to destruct that communication, then it is possible that cancer cells might be starved to death.”
Another challenge is translating research directly into practice, with Pradeep seeing opportunities for women, and their clinicians, to make informed female reproductive health choices but lacking the information to do so.
“Female reproductive health and fitness is still a taboo topic, although it is a very important part of female biology, and essential to women's health and survival,” Pradeep says.
“So not only do we need to continue searching for answers regarding these cancers, but we need to raise awareness about what we find which translates directly to saving lives.”
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