Review the latest research progress of lung cancer

May 1, 2019 / biological Valley BIOON / - lung cancer is the most rapidly malignant disease in recent years, which has the fastest incidence rate and mortality rate, and the most threatening human health and life Among them, the incidence rate and mortality rate of male lung cancer are the first among all malignant tumors Based on this, we summarize the latest research progress on lung cancer to help you understand why lung cancer occurs, why drug resistance and recurrence occur, and what are the latest treatments for lung cancer 【1】 Nature: the immune system attacks growing lung cancer, forcing them to survive through evolution doi: 10.1038/s41586-019-1032-7 In a new study, researchers from the tracerx Alliance (hereinafter referred to as tracerx team) are analyzing how lung cancer evolved in unprecedented detail They did this by tracking 850 patients with the most common form of lung cancer But they know it's not enough to focus on tumors They also explored the environment in which tumors grow This means paying close attention to one of cancer's biggest natural enemies, the immune system The relevant research results were published in the nature Journal on March 28, 2019, and the title of the paper is "noantigen directed immune escape in lung cancer evolution" Image source: LRI EM unit in this new study, tracerx team analyzed samples from 88 cases of early lung cancer that had not yet been treated In addition to observing DNA changes in tumor cells, they also studied how many genetic codes each tumor cell read When DNA is read, part of the genetic code is transcribed to produce RNA molecules, which they then track and measure Tracerx's team found a series of different strategies cancer cells use to escape the immune system These strategies include more durable solutions - such as removing defective DNA fragments that may signal to the immune system - as well as more temporary ones Tracerx's team found that the differences in strategies that tumors evolve depend on the presence of immune cells in the tumor The tumor, which is filled with immune cells, appears to be using temporary strategies to avoid trouble - including preventing certain DNA fragments from being read However, tumor parts with relatively less immune involvement have evolved more durable solutions This helps to build an image of how the tumor adapts to its surroundings For McGranahan and Rosenthal, this is beginning to solve the old debate about how the immune system can promote cancer evolution Tracerx's team can now better understand the intricate relationship between lung cancer and the immune system They came out of the adventure thinking about the future "The positive side is that the immune system is definitely active, or has been active in the past," McGranahan said Therefore, it is possible to reactivate the immune system even if we can only recognize 'cold' tumor areas " This may be a temporary change for cancer cells to escape the immune system However, more research is needed 【2】 Eat more chili! Because the compounds in pepper can stop lung cancer metastasis! Spicy compound from chili peppers slow lung cancer progress a new study shows that the compounds responsible for heat dissipation in pepper may help slow down the spread of lung cancer, which is the main cause of cancer death in men and women Most cancer-related deaths and cancer spread to distant organs, a process known as metastasis "Lung cancer and other cancers usually move to parts of the brain, liver or bone, so it's hard to treat." Jamie Friedman, a PhD student at Dr piyali Dasgupta's laboratory at Marshall University's Joan C Edward School of medicine "Our research shows that capsaicin, a natural compound extracted from capsicum, can be used as a new treatment for lung cancer metastasis." Friedman presented the study at the annual meeting of the American Society for Investigative Pathology during the conference on Experimental Biology held in Orlando, Florida, from April 6 to 9, 2019 In experiments involving three cultured human non-small cell lung cancer cells, the researchers found that capsaicin inhibited the invasion of cancer cells, the first step in the process of cancer cell metastasis They also found that capsaicin fed mice had smaller areas of lung cancer cells that metastasized than untreated mice Additional experiments showed that capsaicin inhibited the metastasis of lung cancer by inhibiting the activation of Src protein This protein plays a role in the signal transduction of cell proliferation, differentiation, movement and adhesion Source: http://cn.bing.com "we hope that one day capsaicin can be combined with other chemotherapy to treat a variety of lung cancer However, clinical use of capsaicin requires overcoming its unpleasant side effects, including gastrointestinal irritation, stomach cramps and burning sensation " Researchers are trying to identify non irritant capsaicin analogues that retain the antitumor activity of capsaicin, and they are also trying to identify natural non irritant capsaicin compounds with antitumor activity 【3】 Nat commun: researchers reveal the root cause of drug resistance of some lung cancer doi: 10.1038/s41467-018-08074-0 researchers from Kanazawa University in nature A new study published in communications shows that Axl (a member of the tyrosine kinase receptor family) can lead to the inherent resistance of some lung cancer patients to ocitinib, and the combination of ocitinib and Axl inhibitors can significantly reduce the resistance of cancer cells to ocitinib Drugs based on tyrosine kinase inhibitors are often used to treat cancer, one of which is called oxitinib, which has been approved for the treatment of lung cancer with EGFR mutation and has certain curative effect However, some patients are naturally resistant to ocitinib, so their response to the drug is poor Seiji Yano and colleagues from the University of Kanazawa now find that Axl causes cancer cells that are resistant to ocitinib, which leads to the resistance of lung cancer to ocitinib The researchers first found that ositinib activated Axl in EGFR mutant lung cancer cells in vitro, and then they found that Axl activity was inversely related to the sensitivity of cells to tyrosine kinase inhibitors Axl expression was related to patients' poor response to ositinib and early recurrence Yano and his colleagues tested whether the drug-resistant cells overexpressed Axl It was found that the survival rate of drug-resistant cells could be reduced by using Axl inhibitor nps1034 at the same time The researchers then looked at the efficacy of Axl inhibitors in combination with ocitinib in the treatment of mice tumors Nps1034 alone has no antitumor effect Only using oxitinib can make the tumor subside, but the tumor will grow again within 7 weeks At the same time, the use of inhibitors and ocitinib can make the tumor stop growing within one week, and the tumor size is stable within 10 weeks No serious side effects were observed during the treatment This finding provides an important molecular mechanism for revealing the tolerance of EGFR mutant lung cancer cells to ocitinib, especially the role of Axl and its inhibitory effect The authors say these results suggest that combination of ositinib and Axl inhibitors may prevent cancer cells from developing resistance to ositinib in the early stages of treatment 【4】 Cancer discov: the ultimate killer of small cell lung cancer! Doi: 10.1158/2159-8290 researchers from Anderson Cancer Center at the University of Texas have found that an immunocheckpoint inhibitor and a targeted therapy to inhibit DNA damage repair (DDR) can significantly inhibit small cell lung cancer in mice The growth of cancer (SCLC) means a potential new method to treat this kind of cancer patients The study, published in cancer discovery recently, shows that olapani, a PARP inhibitor, and other DDR inhibitors can quickly induce immune responses, making SCLC cells that were not sensitive to immunotherapy sensitive Dr Lauren averett Byers, associate professor of internal medicine for chest / head and neck cancer, the study's co-author, said that SCLC is one of the most malignant cancers, accounting for about 15% of all lung cancer patients, and there are 30000 new cases every year in the United States Chemotherapy is the standard therapy for advanced SCLC, but relapse is very common The average survival time of patients is only 12 months Recently, the combination of immunotherapy and chemotherapy has become a new standard, but only a small number of patients can benefit from this new combination therapy The researchers found that DDR inhibitors can activate the immune response of mice, thus increasing the number of tumor killing immune cells This process is controlled by a pathway called sting, which is usually responsible for detecting virus or bacterial infection signals In this study, sting pathway can respond to DNA damage and activate the immune system, ultimately making SCLC cells more sensitive to immunotherapy "I think the results of this study are really surprising because the combination therapy has significantly enhanced the anti-cancer effect I think our findings will benefit our patients " Clinical trials are underway to test PARP inhibitors or immunotherapy for SCLC Byers and his colleagues hope to launch clinical trials by the end of this year to study the efficacy of the combination therapy in humans, and they hope that the therapy will work in other cancer patients with increased DNA damage, such as breast cancer with BRCA mutations and ovarian cancer patients 【5】 Cell Rep: old medicine is new! A class of breast cancer drugs are expected to treat drug-resistant lung cancer! Doi: 10.1016/j.celrep.2018.12.003 Recently, a research report published in the international journal Cell reports, from Francis Scientists from CRIC Research Institute have found that a kind of drug used to treat some breast cancer or to help effectively treat lung cancer resistant to targeted therapy In this paper, the researchers found that when the function of protein P110 α was blocked, the tumor of mice induced by gene EGFR mutation would significantly shrink Drugs that block P110 α have shown great potential in clinical trials for some types of breast cancer, and are expected to be approved for clinical use in the future The latest research results show that these drugs may bring potential benefits to lung cancer patients with EGFR mutations and tolerance to treatment Researcher Julian Professor downward said that in the first few years, targeted therapy was very effective for lung cancer patients with EGFR mutations These drugs have been improving, but unfortunately, after several years of use, cancer began to become tolerant to the treatment and began to spread Currently, the second-line therapy used by lung cancer patients is the conventional chemotherapy method, which is not It is targeted and has serious side effects Photo source: James Heilman, MD / Wikipedia researcher, said that in this study, they would like to further study whether P110 α inhibitor can be used as a new second-line treatment for lung cancer Although the current research is still in the primary stage, later researchers need to conduct more in-depth research on mice and human patients to evaluate the clinical efficacy of this treatment In this study, the researchers targeted the interaction between ras protein and P110 α