Research looks to deny cancer fertile ground in lungs

Paul Mayne // Western News

Alison Allan, a professor of Anatomy & Cell Biology and Oncology at the Schulich School of Medicine & Dentistry, is using the ‘seed-and-soil’ theory in hopes of finding new treatments to halt the metastasis of breast cancer to the lungs.

Alison Allan encounters the reality of her work every day she enters the London Regional Cancer Centre.

“I might see a woman here, same age as me, with a young child, just like me,” said the Anatomy & Cell Biology and Oncology professor at the Schulich School of Medicine & Dentistry. “I walk through the centre to my office and it does provide a sense of urgency, in terms of what we’re doing and to ensure we’re answering the right questions.”

The question currently on her plate is: What about the lungs, one of the most common and deadly sites of breast cancer metastasis (spreading), is so inviting for the cancerous tumours? Allan was recently awarded a three-year, $450,000 grant from the Canadian Breast Cancer Foundation to delve deeper into that mystery.

In her search, she has employed the ‘seed-and-soil’ theory, which proposes patterns of metastasis in specific organs are determined by whether an organ provides the environment (soil) needed by a cancer cell (seed) to start and maintain growth.

Allan’s research studies the lung environment to examine whether specific proteins can mediate breast cancer metastasis. She will identify proteins produced by the lung and released into its environment, and proteins that support lung structure, that may help breast cancer cells travel and spread.

“We’ve made a lot of progress in early detection and surgical techniques,” said Allan, adding if the cancer is caught when it is localized, survival rates are upwards of 80 per cent. “But the problem is, we don’t often know, even at the time of surgery, whether the cells have established themselves in an organ, such as the lungs. It’s that other 20 per cent that do metastasize where there is no cure.”

While the cancerous tumours can travel to multiple places, including the bones, liver and brain, it is the lungs where the more aggressive subtypes of cancer (triple negative and HER2-positive) tend to invade.

“So, not only do we know they’re going to progress faster, we know they’re going to go to the lungs,” said Allan, Assistant Director of the Pamela Greenaway Kohlmeier Translational Breast Cancer Research Unit within the London Regional Cancer Program.

She likened the ‘seed-and-soil’ concept to a dandelion on your lawn. In order for it to spread – and it might go everywhere – it tends to set up shop and grow in congenial soil. One lawn might be dandelion free, while next door is overrun with the weeds.

“There has been a lot of research as to what is inherent about the cancer cells itself, what characteristics it has that might make it want to go there. But no one has really investigated what the lung microenvironment is about – what the soil there, in a sense, is like,” Allan said.

The plan is to examine a pair of proteins, which Allan discovered in previous research, and determine through molecular means if there are inhibitors (drugs) that could interfere with the ability of the lung to provide that ‘optimal soil.’

“The tumour cells will escape into the blood stream and they produce proteins that allow them to eat away at the blood vessels and get into circulation, kind of like getting on the 401,” Allan said. “Then, they exit off to an organ. Once they get to the organ, they decide if they’re going to die, or grow, or occasionally, remain dormant. The hope is we can make it such an unpleasant environment that the cells just die. Hopefully, it doesn’t turn around and go somewhere else.”

But she knows it’s not an easy task.

“The difference with cancer is it is constantly evolving. The idea of survival of the fittest is that these cancer cells, the ones that persist to become metastatic, they adapt. The cancer goes. ‘Screw you,’” Allan said. “If there 10 women with breast cancer, each one will have a different cancer. Cancer at day one is different from cancer in two years.”

Allan is working in conjunction with professor Gilles Lajoie and his Biochemistry group to do proteomic analysis. It is this interdisciplinary work that Allan admits is a plus in the world of research.

“I love my job and the excitement of finding new things, and the partnership we have with the hospitals means the cancer researchers, and others, are right here,” she said. “This means the work we’re doing at the basic science level can be more quickly translated to the clinics. The goal at the end is getting this into patient studies.”