Pillalamarri Srikrishnarka
Chennai, India
Researchers from three different nations concluded in a recent study that air pollution, particularly PM2.5, could be a serious concern for increasing lung cancer patients. They found that ambient air pollution was related to an increased risk of EGFR-driven lung cancer in 32,957 non-smokers and light smokers. In addition, they also discovered that there was a considerable flow of macrophages into the lungs of the mice when the mices were subjected to simulated air pollution. One of their key findings is that even three years of exposure to PM2.5 are enough for a person affected by EGFR-driven lung cancer without DNA damage. This finding has alarmed researchers.
Let’s take a quick look at a few of the fundamental notes I’ve taken to grasp better what cancer is and to study a few of the terms used in the post before we go right into pieces themselves.
Since we know that mutations in healthy cells can cause cancer, the first step in treating the disease is determining what causes these mutations. The initial stage of cancerous development is a step known as the promoter step.
“Epidermal growth factor receptor (EGFR) is a transmembrane protein; overexpression of this factor suggests the presence of cancer, and under expression suggests the possibility of Alzheimer’s. For the identification of this protein, the Nobel Prize in Medicine was conferred.”
Figure 1. (A and B) Representative immunohistochemistry (IHC) images of human EGFRL858R in ET mice exposed to PBS or PM at 10 weeks. C Representative diagram of spatially segmented human EGFRL858R-positive clusters in lung lobes, with the size of clusters proportional to EGFRL858R cell number at 10 weeks. Copyright © 2023, The Author(s), under exclusive license to Springer Nature Limited.
In a credible study, researchers found that the risk of developing lung cancer rose directly to PM2.5 in the air. They also found that this pattern held throughout all of the East Asian nations studied, in contrast to the native population of the UK.
For researchers to obtain further clinical insights into the progression of lung cancer, they genetically changed a few mice, caused cells to begin the mutation process, and then subjected the animals to ambient air pollution for ten weeks. Due to the exposure to PM, they observed an increase in the adenocarcinomas and aggressive CCSP-rtTa; TetO-EGFR model of doxycycline inducive hyperplasias in an adenoviral-CMV-Cre Kras model of lung cancer.
“They eventually concluded that exposure to PM promotes tumour progression in both oncogenic Kras and EGFR models of lung adenocarcinoma tumours.”
In addition, the evidence that was provided about the clonal dynamics shows that because of PM exposure, EGFR mutant cells grow with the capacity to form a tumour, and an increase in the proliferation rate of EGFR mutant cells demonstrates this.
The IL-6-JAK-STAT pathway is responsible for the mutation, which begs the question, “How does the mutation take place?” Only after exposure to PM were the immune response pathways of inflammation and the allograft response pathway shown to be elevated. Because of the exposure to PM, the expression of the genes for interleukin-1beta (IL-1beta), GM-CSF, CCL6, NK-kB, and epithelial-derived alarmin IL-33 increased. AT2 cells are a candidate cells for the beginning of the adenocarcinoma process in the lung.
“When exposed to PM, lung macrophages release inflammatory cytokines, which is central for tumour promotion. In addition, the IL-1beta signaling is required to promote PM-mediated EGFR-driven lung adenocarcinoma.”
The researchers went on to verify this notion using human lung tissue from 195 people who did not have cancer. They discovered that EGFR-driven mutations might be present in histologically normal lung tissues, even in patients who did not have the same mutations picked during the NSCLC carcinogenesis process. This suggests that EGFR can cause mutations in lung tissue.
The presented data is extremely concerning, and immediate urban replanning is required to stop the further growth in air pollution. However, it is not a sustainable solution to protect oneself from air pollution by donning a mask; rather, a concerted effort by scientists, engineers, city planners, medics, and people in general to battle air pollution is the way ahead.
Reference:
Hill, W., Lim, E.L., Weeden, C.E. et al. Lung adenocarcinoma promotion by air pollutants. Nature 616, 159–167 (2023). https://doi.org/10.1038/s41586-023-05874-3