Lung cancer progression can be predicted by the tumor stroma

Squamous cell carcinoma (SqCC) is the second most common type of
lung cancer.
However, treatment options for these patients remain limited and largely unchanged
for decades.
Now, a new study by researchers at the Garvan Institute of Medicine has identified a molecular map of the stroma surrounding squamous cell carcinoma, which may indicate which patients may develop aggressive tumors
.

Their findings, "Extracellular matrix mapping determines risk and prognosis of squamous cell carcinoma subtypes of non-small cell lung cancer," were published in the journal BMC Genomic Medicine
.

"SqCC is a subtype of non-small cell lung cancer, and patients still have a poor
prognosis," the researchers wrote.
"The extracellular matrix (ECM) is essential in regulating cellular behavior; However, its importance in tumor aggressiveness remains to be fully studied
.
”

Dr Amelia Parker, first author of the study, explains: "Our focus is on how the stroma changes in squamous cell lung cancer, how this may make tumors more aggressive, and how it can be used to help understand patient outcomes
.
"

"A tumor is an ecosystem made up of cancer cells linked together by a stroma, which we believe is the stroma that supports the continued growth and spread of cancer cells, leading to poor
prognosis for some patients.
" But we don't really understand what the matrix looks like or why it makes lung cancer resistant to treatment
.
If we can understand this part of the tumor, we can find more effective treatments that target the stroma to make the cancer more aggressive
.
”

These findings could potentially be used to develop biomarkers to determine which patients might benefit
from more aggressive and targeted treatments.

The researchers studied the molecular and protein composition
of the matrix surrounding the tumor in lung squamous cell carcinoma extracted from patient tissue samples.

"This analysis reveals subtype-specific ECM features associated with tumor initiation that can predict premalignant progression
," the researchers wrote.
"We found that an ECM-rich tumor subtype was associated with
the worst prognosis.
In silicon analysis, it was shown that the matrix remodeling program activates intracellular signals to varying degrees in tumors and stromal cells to enhance matrix remodeling
associated with drug resistance and progression.
The stromal subtype with the worst prognosis resembles ECM remodeling in idiopathic pulmonary fibrosis and may represent a cancer area
associated with increased cancer risk.
”

The team also found that while adenocarcinoma and squamous cell carcinoma are clinically similar, their matrix composition is very different
.
These differences have the potential to be exploited
by existing therapies for other diseases.

"The two tumors look very similar under the microscope and are usually treated with the same approach, but very different at the molecular level," said
Dr.
Thomas Cox, associate professor and director of Garvan's Matrix and Metastasis Laboratory.
"This explains why some patients are progressing well and others are not, and how we can stratify patients to provide more personalized treatment
.
"

As a next step, the researchers are seeking to conduct a clinical trial with clinical partners to repurpose treatments that may prevent this matrix remodeling in lung cancer patients and improve treatment response
.