Some mutations that provoke lung cancer can be used to develop antitumor immune therapy, according to an article on the website of the journal Science and Life..

According to the World Health Organization (WHO), lung cancer is the most common oncological disease: it accounts for about 1.5 million cases of oncological diagnoses annually, of which 85% are the so-called non-small cell lung cancer.. It is mainly represented by two types: adenocarcinoma and squamous cell carcinoma of the lung..

Both of them - adenocarcinoma and squamous cell carcinoma - although related to each other, are still quite different from each other.. Matthew Meyerson, a senior research fellow at the Broad Institute, and an international team of researchers led by him, including Anton Alexandrov, a PhD student at the St. Petersburg University of Information Technology, Mechanics and Optics (ITMO), published an article in the latest issue of the journal Nature.

Differences and similarities between different tumors were found as a result of genetic analysis of 1144 cancer samples taken from patients with adenocarcinoma and squamous cell carcinoma of the lung.. As you know, cancer occurs as a result of mutations in DNA, but if we consider all the mutations that have occurred in tumor cells, we will see among them those that are simply present in the process of cancer growth, not being its cause (“passenger” mutations),.

The authors of the work were primarily interested in driver mutations.. Separating them using statistical analysis methods from “passenger” mutations, it was possible to detect 38 highly mutated genes in adenocarcinoma and 20 in squamous cell carcinoma.. However, only 6 of them were common for both types of tumors, which suggested that, although both types of cancer originate in the same organ, they are very different from each other..

It was previously thought that for adenocarcinoma and squamous cell carcinoma of the lung, significant driver mutations would be the same, but it turned out that everything is more dependent on the original cell type.. In the future, the researchers plan to find the factors that determine the fate of the mutation - in other words, why in one type of cell a defect in DNA causes uncontrolled growth, and in another type of cells nothing happens with the same mutation.. This will allow researchers to develop more effective drugs, says Joshua Campbell, research fellow at the Broad Institute and lead author of the paper..

In addition, the researchers have identified a number of mutations that can be used to develop new methods of targeted (target - target, target) and immune therapy.. Immunotherapy has a potential advantage over chemotherapy and radiotherapy because it targets the tumor without affecting healthy cells.. Mutant changes in proteins often turn out to be part of epitopes - the so-called fragments of molecules that the immune system can “see”. This new epitope (neoepitope) allows the immune system to recognize the protein on the malignant cell and then attack it..

47% of adenocarcinoma samples and 53% of squamous cell carcinoma samples were found to have at least 5 neoepitopes, suggesting a high potential for immunotherapy to fight lung cancer. Actually, the essence of immune therapy is to tell the immune system what to pay attention to.. “Creating targeted cancer vaccines is based on teaching the immune system to attack cancer cells on its own.. We have identified several different repeat mutations that can be detected by the immune system, making them prime candidates for treatment with these vaccines,” says Joshua Campbell.

With the help of bioengineering methods, it is possible to design molecules that will carry fragments of cancer proteins (the same neoepitopes) and which at the same time will be easily read by cells and molecules of the immune system..

“The cell is constantly presenting pieces of proteins called epitopes to the immune system for inspection.. If for some reason the immune system was unable to capture the epitope of the mutated protein and missed it, then a tumor may occur.. Identification of epitopes that the immune system of a particular patient needs to detect is important for developing an individual cancer treatment strategy.. Attaching neoepitopes to proteins will tell the body’s immune system where it needs help,” says ITMO University research engineer Anton Aleksandrov, who developed software for immunological research. Its essence was to optimize the operation of a whole set of third-party programs that are used in the course of computational determination of the immunogenicity of mutations..

Of course, the authors of the work could not get around one of the most pressing issues regarding lung cancer, namely, how lung cancer and smoking are related.? By assessing the number of mutations induced by cigarette smoke in each sample, the researchers found that adenocarcinoma of the lung is one of the tumors in which only a small proportion of mutations are associated with smoking.; in addition, samples of this tumor were mainly taken from people who had never smoked. The results obtained are also supported by epidemiological data, which in general speaks in favor of the assumption that lung cancer may arise under the influence of other primary factors not related to smoking..

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