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Recently, the top academic journal "Cell" published a study on lung cancer, examining the biological basis of lung squamous cell carcinoma (LSCC), a type of lung cancer with few treatment options and high fatality rate.
In-depth elaboration, to find a number of potential new drug targets in order to overcome this type of cancer, as well as to help improve the effect of immunotherapy regulatory pathways
.
In this study, researchers from the Broad Institute and many other institutions carried out proteogenomic research on lung squamous cell carcinoma, that is, using genomics, transcriptomics, proteomics, imaging and clinical data for Lung squamous cell carcinoma has drawn the most comprehensive molecular map to date
.
The data of this study is currently available for free through the relevant website of the National Institutes of Health (NIH): https://proteomics.
cancer.
gov/data-portal
.
The research team collected 108 cases of lung squamous cell carcinoma before treatment, analyzed the DNA, RNA, protein and protein post-transcriptional modifications (such as phosphorylation, acetylation, ubiquitination, etc.
), and compared 99 cases of cancer.
The samples of normal tissues nearby were compared
.
▲Study diagram (picture source: reference [1])
The researchers pointed out that many clinical trials for lung squamous cell carcinoma have failed in the past.
A deeper understanding of the biological basis of this cancer will reveal new opportunities for the treatment of lung squamous cell carcinoma
.
For example, FGFR1 is a gene frequently amplified in lung squamous cell carcinoma.
There are also some tumors with low expression of p63, showing high expression of survivin
.
The latter is a protein that regulates cell proliferation and death.
The data also shows that targeting the two targets of LSD1 and EZH2, which regulate chromatin, is beneficial to the treatment of tumors driven by the overexpression of the transcription factor SOX2
.
This result means that SOX2, which itself is often regarded as a "non-drugable" target, can be a different way
In addition to the above-mentioned potential drug targets, protein genomics also provides a lot of immune-related data, pointing out the direction for exploring better immunotherapy
.
The researchers mentioned that although immunotherapy has benefited many lung cancer patients in the past few decades, for lung squamous cell carcinoma patients, only a few showed long-term responses
Some of these data highlight the biomarkers related to immune checkpoint inhibitors (such as PD-1 inhibitors) and immune evasion in certain tumors, and provide some clues for understanding the different prognosis of different lung adenocarcinoma patients on immunotherapy.
.
Another important finding of this research is a new molecular subtype of lung squamous cell carcinoma
.
Previously through genomics, scientists have identified four molecular subtypes of lung adenocarcinoma, corresponding to different cell types and development processes
In addition, the research data also provides new insights into the disease mechanism of lung squamous cell carcinoma, showing the relationship between ubiquitination, phosphorylation, acetylation and other metabolic pathways that are disordered and interfering with each other to drive tumorigenesis
(Image source: Reference [1])
Note: The original text has been deleted
Reference
[1] Shankha Satpathy et al.
[2] A more complete molecular picture of lung squamous cell carcinoma comes into view.
Retrieved Aug.
