Research uncovers molecule pivotal in making ovarian cancer cells so lethal

Fall 2015

Thousands of women are living with ovarian cancer across North America.  It is estimated that this year alone, 2,800 Canadian women will be newly diagnosed with the disease.  And even though ovarian cancer continues to be one of the most serious women’s cancers, there is a lack of reliable early detection tests and few treatment options.

Lawson Health Research Institute’s Dr. Trevor Shepherd, a research scientist at the Cancer Research Laboratory at LHSC, is one of a handful of scientists in Canada to dedicate his career to finding a cure for ovarian cancer. His latest findings bring new hope for improved treatments.

The Silent Killer

Ovarian cancer, often called “The Silent Killer”, is one of the most deadly cancers in women.  According to the Canadian Cancer Society, only 20-30 per cent of women diagnosed with late stage ovarian cancer are alive five years later.  Think of it this way: if there are 10 women with ovarian cancer in a room, only two or three of them will be alive in five years.

Why? There are no good routine screening tests for early or late detection of ovarian cancer.  Furthermore, it is usually found at a very advanced stage because there are few symptoms that draw a woman’s attention to the fact that something is wrong.

By the time of diagnosis the majority of women already have extensive spread of the disease which makes it difficult to treat by surgery or chemotherapy.  According to Dr. Shepherd, what is even more concerning is the propensity of the disease to keep coming back until it is eventually resistant to therapy.

In order to find out how and why ovarian cancer cells grow and take on such lethal characteristics, Dr. Shepherd and his team grow the cancer cells in 3D structures, called “spheroids” – the same way the cancer cells grow in patients. 

Spheroids are sticky and can attach themselves to different organs, such as the uterus, liver, stomach or small intestine.  Here they can sit dormant and unnoticed for months or years before growing and becoming resistant to chemotherapy. 

However, a surprising new finding by Dr. Shepherd and his team at Lawson has identified a new target for ovarian cancer therapies.

The Jekyll and Hyde molecule

Recently, Dr. Shepherd’s lab discovered that the spheroids activate a ‘stress signal’, and the major molecule controlling this signal is called LKB1.

Previous studies stated that LKB1 was a tumour suppressor in ovarian cancer, meaning that tumour cells need to get rid of LKB1 to cause cancer, but Dr. Shepherd’s work is in direct conflict with these studies. 

Their study definitively shows that ovarian cancer cells still have LKB1 and that this molecule allows ovarian cancer spheroids to change their metabolism, promote tumour cell survival and make them more resistant to chemotherapy.

“To get to metastatic cancer - cancer that has spread from one location in the body to another - cells go through a lot of changes,” says Dr. Shepherd. “They can change as the disease progresses from its early to late stages.”

And while in early stages of cancer LKB1 may serve to suppress cancer, the researchers have shown that the molecule can be co-opted by late stage ovarian cancer cells to increase resistance to chemotherapy. This ability to shift roles so drastically likens LKB1 to a potential ‘Jekyll-and-Hyde’ molecule.

“What we have here is a huge opportunity to develop a therapeutic treatment that targets LKB1,” says Dr. Shepherd. “Blocking these molecules could potentially kill ovarian cancer cells.”

By refuting the previous studies, Dr. Shepherd has uncovered a new target for future therapy.

What’s next?

Currently, Dr. Shepherd’s team is focused on further understanding the role of the LKB1 molecule. The team is also forming a collaboration with the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital in Toronto that will speed identification of chemicals that effectively target LKB1.

“We need to move on this quickly,” Dr. Shepherd says.

His hope is to find a targeted therapeutic that can be used in conjunction with chemotherapy to form a multipronged approach for improved treatment of ovarian cancer.

Lawson Health Research Institute is the research arm of London Health Sciences Centre and St. Joseph’s Health Care London, and is one of the top 10 hospital-based research institutes in Canada.

 

 

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Dr. Trevor Shepherd is one of a handful of scientists in Canada to dedicate his career to finding a cure for ovarian cancer.