Tumour matrix profiling can predict some lung cancers' progression

SYDNEY: A common type of lung cancer has molecular profiles of its surrounding matrix that have been uncovered by researchers at the Garvan Institute of Medical Research. These profiles may help identify which patients are most likely to experience aggressive tumour growth. As far as lung cancer goes, squamous cell carcinoma is the second most common variety. But over the years, the range of available treatments for these people has stayed substantially unchanged. Less than one in five patients will live more than five years after their diagnosis because of high rates of recurrence and drug resistance.

Researchers at Garvan have been focusing on the environment that surrounds these cancer cells in the tumour in addition to researching the cancer cells themselves. A major component of this environment is the extracellular matrix, a 3D meshwork of around 300 core molecules. This matrix is present in all tissues in the body, where it normally provides structural and functional support to hold cells together. But in cancers, this matrix is fundamentally altered and these changes can promote tumour growth.

"Our focus was on how the matrix is changing in squamous cell lung carcinoma, how this might make tumours more aggressive, and how it could be used to help with understanding patient prognosis," says Dr Amelia Parker, first author of the study. "Tumours are an ecosystem, made up of cancer cells held together by the matrix - it is this matrix that we think is supporting cancer cells to keep growing and spreading, contributing to the poor outcome for some patients. But we didn't really have an understanding of what the matrix looks like or why it makes lung cancer resistant to treatment. If we can understand that part of the tumour, we can reveal more effective ways to treat patients by targeting the way the matrix is making cancer more aggressive."

The research, which was published in BMC Genome Medicine, may be used to create biomarkers that can help doctors decide whether patients would benefit from a more aggressive and specific treatment. The group, under the direction of Associate Professor Thomas Cox, examined in detail the protein and molecular makeup of the matrix around squamous cell carcinoma lung tumours using patient tissue samples.

They discovered two tumour matrix characteristics, one with favourable patient outcomes and the other with unfavourable outcomes. These matrix profiles seem to form early in the development of the tumour and endure as it grows, dictating how the tumour will react to chemotherapy. Greater collagen proteins and more fibrosis, or hardening of the tumour structure, were found in the tumour matrix of patients who did poorly, indicating that the tumour matrix changes to fend off therapy.

The scientists also discovered that although adenocarcinomas and squamous cell carcinomas look similar in the clinic, their matrix compositions differ significantly. Existing medicines created to treat other diseases may be able to take use of these differences. "These two tumours look very similar under the microscope, and are typically treated the same way, but are very different on a molecular level," says Associate Professor Cox, head of the Matrix and Metastasis lab at Garvan. "This sheds light on why some patients progress well and others don't, and how we might be able to stratify patients to provide more personalised treatment."

The next step is to engage with clinical partners to move toward a clinical trial for repurposing therapies that may prevent this matrix remodelling in lung cancer patients, and improve response to therapy.