Two Cell interpretations! A comprehensive analysis of the proteinological properties of lung cancer may help develop a new type of personalized lung cancer therapy.

!--:pagetitle"--July 29, 2020 -- Lung cancer is the world's most commonly diagnosed type of cancer and the leading cause of cancer-related deaths, killing more people each year than breast, colon and prostate cancer combined.
although the genome provides a lot of information, it can only provide single-dimensional information about the inner workings of cancer cells, and in a study published in the first cell journal, scientists from the MIT Broad Institute and others say they used a proteomic method that combines the genome with a complete proteomics to reveal how mutations that drive lung cancer affect the activity of key proteins, while the researchers also discovered a new interaction between lung tumors and the immune system.
these findings may provide an opportunity for researchers to develop new lung cancer treatments and help to better understand the biological mechanisms of lung cancer.
photo source: NCI researcher Michael Gillette says genes may provide a blueprint, but ultimately proteins are the engine of biology, and accurately describing cancer proteomics and their post-translation modifications is critical to understanding key therapeutic innovations.
, researchers studied 110 patients with lung adenocarcinoma, a non-small cell lung cancer that included patients from eight countries, representing different ancestors, as well as patients with a history of smoking and non-smoking.
in the lab, the researchers thoroughly and systematically analyzed the composition, activation status (measured by the phosphoryeof of proteins), the characteristics of other post-translation modifications (including acetylation modification, etc.), and matched the data to mutations and other characteristics of each tumor genome, while comparing the data with normal lung tissue in each patient;
these studies provide a number of unique observations that are not visible in genomics alone, for example, the researchers' analysis also found that lung adenocarcinoma has a fourth, so far undefined molecular subtype with unique biological signals and immune response characteristics, which may have some clinical relevance.
researchers found that there may be high activation of specific key proteins in tumors carrying ALK fusion or EGFR or KRAS mutations (three driving mutations common in lung adenocarcinoma), and described the downstream effects of driving mutations on the expression, phosphorylation, and acetylization of multiple cancer-related proteins, noting that PTPP N11 (SHP2) proteins are frequent and highly activated in ALK fusion and EGFR mutation-driven tumors, and PTPN11 is a known therapeutic target, and research data suggest that patients with genomic abnormalities in tumors may benefit from treatments that reduce the activity of PTPN11.
related findings may also extend to the immune microenvironment inside the tumor, revealing features that may help explain multiple aspects of the body's immune response to tumors and indicate potential targets for immunomodulation therapy, as the researchers note that immuno""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""""--
, the researchers found that some immune "hot" tumors (actively immersed by immune cells) actually build their own defense systems and fill themselves with immunosuppressive cells to avoid the host's defensesystem, a subset of which also increases the production of IDO1 and CTLA4 factors, which act as immune cell brakes, so immunotherapy that suppresses these targets may allow patients to respond successfully.
by comparing tumors and normal tissue in people with a history of smoking and non-smoking, the researchers identified different pathways of expression in tumors in smokers and non-smokers, which could provide scientists with new biological insights at the DNA or RNA level, further highlighting the added value of proteinization, and the researchers noted that the ARHGEF5 protein may also be a potential target for non-smoking populations. All of this emphasizes that truly understanding the deep nuances of biology requires incredible integration, cross-molecular analysis, and cross-disciplinary collaboration, so these areas must come together to help researchers develop strategies that benefit patients,
, says Gillette, a researcher at the
.
another study published in the journal Cell, researchers conducted a supplementary study of lung cancer patients in East Asia, using protein genomics and precision oncology to help fight cancer, studying novel lung oncology, or effectively driving scientists to develop new strategies to diagnose lung cancer and manage patients.
researcher Satpathy points out that research and databases may accelerate the transformation of laboratories into clinical practice, and now researchers are considering whether they can build resources for inflammation or answer ingenual cancer biology and specific questions, while emphasizing the value and significance of proteomics' full understanding of tumor biology, which is not based solely on genomics, and which could help researchers identify new potential therapeutic targets and help create a sustainable mechanism to benefit lung cancer patients.
() Source: "1" Lung cancer proteome builds on genetic speds to reveal therapeutic strategies !--/ewebeditor: page- !--ewebeditor: page title"--2 Michael A. Gillette, Shankha Satpathy, Song Cao, et al. Proteogenomic CharacterIzation Reveals Vulnerability Therapeutics in Aden Aden arcamcinoma, Cell (2020). doi: 10.1016/j.cell.2020.013 3 Yi-Ju Chen, Chen, Theodoros I. Roumeliotis, Ya-Hsuan Chang, et al. Proteogenomics of Non-smok-smoking Lung Cancer in East Asia Delineates Ses S. Moleculars of Origines and Progression, Cell (2020.doi:10.1016/j.cell.2020.012.!--.012