Unravelling the cause of breast cancer progression

Breast cancer is the most common cancer affecting Canadian women. Advancements in treatments have helped many women diagnosed with breast cancer overcome the disease. Unfortunately, some still succumb to the illness because their cancer is resistant to treatment and has spread to other parts of the body. These breast cancer patients require new, effective treatments to improve their survival. The development of such therapies will require increased knowledge of how and why breast cancers grow and spread at the cellular level.

The Marcato lab at Dalhousie University is fighting breast cancer from multiple angles. One angle is to study a class of molecules called long non-coding RNAs.

Dr. Marcato (centre) with members of her lab – photo provided

Long non-coding RNAs, or lncRNAs are emerging as important regulators of cancer growth, spread, and drug resistance. The goal of Dr. Paola Marcato and her team is to expand the knowledge of how lncRNAs regulate these critical processes. The team had an idea of how lncRNAs work, by interacting with other RNAs and other molecules in the cell. The lncRNA they are studying can cause the cancer cell to hide from the immune system, grow faster, and spread.

“When we knockdown or reduce the lncRNA, it has the reverse effect, meaning that the immune cells can now find the cancer cells”, explains postdoctoral fellow Dr. Jaganathan Venkatesh. And hopefully tumour eradication.

Exploring the role of lncRNAs in cancer is a new area of research interest for Dr. Marcato. “I kept seeing lncRNAs coming up in our analyses of breast tumour genomics data and wondered what they were doing.”, says Dr. Marcato. “It piqued my interest.” LncRNAs are an untapped area that could be harnessed to develop novel therapeutics if scientists can understand what these molecules are doing in cancer.

Dr. Marcato’s recent PhD graduate student and CRTP trainee Marie Claire Wasson is also highly involved in the lncRNA research project. “We don’t know what a lot of these lncRNAs are doing, but at least some are key mediators of cancer development and progression” explains Dr. Venkatesh. “There are as many lncRNA genes as protein genes, and we need to know which ones to develop therapeutics against. We need to find out which lncRNA genes are really bad for patients and cause tumours to grow and spread.” Dr. Marcato, with Dr. Venkatesh and Dr. Wasson, screened thousands of lncRNAs and eventually identified one that they believe holds significant promise as a novel therapeutic target. Dr. Venkatesh continues to perform experiments to understand the function of this lncRNA in cancer and design drugs to target these lncRNA, “We believe lncRNA research holds much promise for the development of future cancer therapies.” 

Supporting novel research

A BHCRI seed grant to Drs. Marcato and Venkatesh provided initial funding for the team to conduct preliminary experiments on which an application to the Canadian Institutes of Health Research (CIHR) rested.  “The impact of this seed funding from BHCRI has been very significant,” says Dr. Marcato. “It allowed us to generate critical preliminary data to apply for a CIHR grant which was successful.” This was Dr. Marcato’s first seed grant from BHCRI and it allowed her to take her research in a new direction. Supporting novel research is one of the main goals of the Seed grant program. Grant applications to agencies such as CIHR require lots of preliminary data. That is the purpose of seed grants; to allow investigators to explore novel ideas and gain valuable data to support applications going forward.  is critical. “As a mid-career investigator, I don’t have access to start-up funds,” says Dr. Marcato.  For us, we tried everything we could to get funded”. As with many funding competitions, it takes perseverance. For Marcato, it took three tries to get her CIHR. “I submitted it [the application for funding] but knew I didn’t have enough data to get the CIHR funding. Because of the seed grant from BHCRI, we were able to generate critical data that allowed us to get the [CIHR] grant. The reason we’ve been successful is because of local money,” says Dr. Marcato.  “This has kept us going and helped us get bigger. It’s critical we keep this local funding.”

Dr. Marcato’s research will provide new information and fundamental insights into how lncRNAs promote breast cancer growth and spread. “Our findings will have a meaningful impact on our understanding of cancer and identify a novel drug target to develop more effective treatments”, reports Marcato. “Our work will ultimately lead to improved survival outcomes for patients.”

The field of lncRNA is a huge growth area and the Marcato lab is one of the few research labs in Canada studying these molecules, with the ultimate aim of developing cancer therapeutics.

“We have a huge opportunity right now, with this new CIHR funding for the next five years. Over the next few years, we can really do something big but can’t get complacent in submitting grant applications. We all have to be proactive and push.”

Members of the new five-year, $1M CIHR grant include Drs. Penny Barnes, Gillian Bethune, Jeanette Boudreau, Shashi Gujar, Jaganathan Venkatesh (CRTP Postdoctoral Fellow), and Marie-Claire Wasson (CRTP graduate student).

To support exciting cancer research like Dr. Marcato’s, visit: https://alumniapps2.dal.ca/giving/?gift=bhcri