Tumor matrix profiling offers clues to progression of some lung cancers

Tumor matrix profiling offers clues to progression of some lung cancers

Graphics of lungs and cells. Credit: Thomas Cox/Garvan Institute

Scientists at the Garvan Institute for Medical Research have determined that the molecular configuration of the surrounding matrix of a common lung cancer can indicate which patients are more likely to develop melanoma.

Squamous cell carcinoma is the second most common type of lung cancer. However, the treatment options for these patients remain limited and have remained largely unchanged for decades. High rates of relapse and chemotherapy resistance mean that less than one in five patients will survive more than five years after diagnosis.

In addition to learning cancer cells, the Garvan researchers turned their attention to the environment surrounding these cancer cells within the tumor. A major component of this environment is extracellular matrix, a 3D lattice of about 300 core molecules. This substrate is present in all tissues in the body, where it normally provides structural and functional support for holding cells together. But in cancer, this matrix is ​​fundamentally altered, and these changes can promote tumor growth.

“Our focus is on how matrix changes in squamous cell lung carcinoma, how this can make the tumor more malignant and how it can be used to help understand patient prognosis“, said Dr Amelia Parker, first author of the study.

“Tumors are an ecosystem, made up of cancer cells linked together by a matrix—we think it’s this matrix that’s helping cancer cells continue to grow and spread. wide, contributing to poor outcomes for some patients. But we really don’t have an understanding of what the matrix looks like or why it makes lung cancer resistant to treatment.”

The findings, published in Genomic Medicinecould potentially be used to develop biomarkers to identify which patients might benefit from more aggressive and targeted treatments.

The team led by Associate Professor Thomas Cox comprehensively studied the molecular and protein composition of the surrounding substrate. squamous cell carcinoma lung tumor, taken from the patient’s tissue samples.

They identified two tumor matrix profiles — one with a good prognosis and the other with a poor progression. These matrix profiles appear to be established early in tumor formation and persist as the tumor grows, controlling how the tumor will respond to chemotherapy treatment.

Tumor matrices in patients with worse condition had more collagen protein and more fibrosis—hardening of the tumor structure—suggesting that the tumor matrix would restructure to protect itself from the disease. treat.

The team also found that, while adenocarcinoma and squamous cell carcinoma appear similar in the clinic, they are completely different in matrix composition. These differences have the potential to be leveraged by existing therapies being developed to treat other diseases.

“These two tumors look very similar under the microscope and are often treated in the same way, but are very different in Element Level“, said Associate Professor Cox, head of the Matrix and Metastasis laboratory at Garvan. “This sheds light on why some patients do well and others don’t, and how we have can stratify patients to provide a more personalized treatment.”

The next step is to engage with clinical partners to move toward a clinical trial to repurpose therapies that can block this matrix remodeling in lung cancer patients and improve response to cancer. therapy.

More information:
Extracellular matrix profile Risk determination and 1 prognosis of the squamous cell carcinoma subtype of non-small cell lung carcinoma, Genomic Medicine (2022). DOI: 10.1186/s13073-022-01127-6

quote: Tumor matrix records giving clues to progression of several lung cancers (2022, 20 November) retrieved 20 November 2022 from 2022-11-tumor-matrix-profiling-clues-lung.html

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