New protein discovery could aid in lung cancer treatment

According to a recent study, the levels of a protein named "TLR2" in tumors can indicate whether a patient would survive after being diagnosed with lung cancer, according to a press release published by the University of Edinburgh.

A collaboration of researchers from the University of Edinburgh, University College London, the University of Cantabria in Spain, the Spanish National Research Council, and the Mayo Clinic in the USA tested a drug compound that activates TLR2 in mice and found it can slow down the growth of the disease in the early stages.

Controlling some of the body's defense mechanisms

The research team discovered that TLR2 aids in regulating some of the body's defense mechanisms when cancerous mutations take place in cells.

TLR2 is associated with senescence, a process when cells stop growing and secrete a range of chemicals and other proteins that act as alarms and barriers against cancer. Senescent cells are present in early lung tumors, but they disappear in late-stage cancers, which suggests that senescence can stop the progression of cancer.

After being sure of the significance of TLR2, the research team used data from human tumor samples. They eventually observed that people with higher levels of the TLR2 protein in the early stages of lung cancer show higher rates of survival when compared to those with lower levels.

The team next tested a medication that has been shown to activate TLR2 in a mouse model of lung cancer. Researchers discovered that the medication slowed the growth of lung tumors.

"I think these results are really exciting. Very little is known about the biology of early lung cancer and by understanding this process more we have identified a possible new treatment for this devastating disease. This project highlights the value of basic science research and how this can be translated into new treatments for patients," said Dr. Fraser Millar Clinical lecturer in Respiratory Medicine at the University of Edinburgh.

Paving the way for further research

Experts are hopeful that these discoveries will spur research into the use of senescence and the related compounds that are secreted as a screening tool to detect lung cancer early.

The team notes that additional investigation, such as clinical trials, is required to determine whether the medication is useful in people.

The study was published in Cell Reports.

Study Abstract:

Targeting early-stage lung cancer is vital to improve survival. However, the mechanisms and components of the early tumor suppressor response in lung cancer are not well understood. In this report, we study the role of Toll-like receptor 2 (TLR2), a regulator of oncogene-induced senescence, which is a key tumor suppressor response in premalignancy. Using human lung cancer samples and genetically engineered mouse models, we show that TLR2 is active early in lung tumorigenesis, where it correlates with improved survival and clinical regression. Mechanistically, TLR2 impairs early lung cancer progression via activation of cell intrinsic cell cycle arrest pathways and the proinflammatory senescence-associated secretory phenotype (SASP). The SASP regulates non-cell autonomous anti-tumor responses, such as immune surveillance of premalignant cells, and we observe impaired myeloid cell recruitment to lung tumors after Tlr2 loss. Last, we show that administration of a TLR2 agonist reduces lung tumor growth, highlighting TLR2 as a possible therapeutic target.