Sometimes, it is called the lungs of adenocarcinoma will produce anti-drug resistance to the initial successful treatment and transform into a more aggressive cancer, that is, that is,Small cell lung cancer (SCLC), such cancer spread rapidly and limited treatment plans.Scientists at Wil Cornell Medical School have created a mouse model that reveals this challenging phenomenon called histological transformation.This research deepen our understanding of how genetic mutations promote the progress of cancer and find potential targets for more effective therapies.
Researchers captured transformed clues: Immune fluorescent images show that small cell lung carcinoma (purple pink) in mice lung (Green) diffuses, bronchial contains residual pulmonary adenocarcinoma tumor cells (blue).Image source: Dr. Eric Gardner of the Wrast Laboratory
Researchers research results were published in Science magazines. They found that they were from the lungs.During the transition of adenocarcinoma to small cell lung cancer (SCLC), mutant cells seem to change cell identity through an intermediate state similar to stem cells, thereby promoting transformation.
"It is very difficult to study this process in human patients. Therefore, my goal is to reveal the inherent mechanism of the transformation of lung adenocarcinoma to small cell lung cancer in mice models." ResearchDr. Eric Gedner, the leader, said that he was a professor of medical professor of Lewis-Thomas University, Sandra and Edward Miye Central Member of HaroPost-doctoral researcher at Dr. De-Valamus Laboratory.This complicated mice model took several years to develop and qualitatively developed, but the researchers cracked this problem.
This research is Dr. Ashley Laughney, a assistant professor professor with physiology and biophysics, and a member of the Miye Cancer Center, a member of the Wil Condon Medical College.As well as Graduate Students of Lotney Labs and Ethan Earlie, a member of the third hospital computing biology and medical projects, Ethan Earlie.
Dr. Wramus said: "As we all know, cancer cells will continue to evolve, especially to avoid the pressure of effective treatment.The combination of molecular features) with computer -based data analysis can depict dramatic complex events during the evolution of fatal cancer and reveal new treatment goals.Those with severe smokers, but this type of tumor also occurs on quite a lot of patients with lung adenocarcinoma, especially after receiving a protein called (EGFR)This protein can promote tumor growth.The new SCLC tumors anti-epidermal growth factor receptor therapy has resistance, because their growth is driven by a new cancer-driven factors-high-level MyC protein.
In order to reveal the interaction between these cancer pathways, the researchers designed mice to suffer from a common lung adenocarcinoma. In this kind of cancerDriver of growth factor receptor gene mutation.They then turned adenocarcinoma tumors into SCLC tumors, which usually come from nerve endocrine cells.To this end, they closed the epidermal growth factor receptor, and other changes have also occurred, including the lack of tumor inhibitory gene RB1 and TRP53, and the proliferation of known SCLC driving genes myc.
Cancer genes such as epidermal growth factor receptor (EGFR) and MYC are the variation forms of normal control cell growth genes.They are well known in promoting cancer growth and diffusion.On the other hand, cancer suppression genes usually inhibit cell proliferation and tumor development.
Surprisingly, this study shows that the way of carcinogenic genes is related to the environment.Although most lung cells have resistance to the carcinogenic effects of MyC, nerve endocrine cells are very sensitive to the carcinogenic effects of MyC.Instead, the epithelial cells of the lung airbags are the forethers of lung adenocarcinoma, and they grow excessively under the action of mutation of epidermal growth factor receptor.
Dr. Laughney said: "This shows that in the wrong cell type, the" cancer gene no longer plays a roleThe view of carcinogenia. "
Researchers have also discovered a stem cell -like intermediate that neither adenocarcinoma nor SCLC.Only when the tumor inhibits gene RB1 and TP53 mutations, the cells in this transition state will become nerve endocrine cells.They observed that the lack of tumor inhibitory factors called PTEN accelerated this process.At this stage, carcinogenic genes myc can drive these intermediate stem cells to form SCLC tumors.
This research further supports the efforts to find targeted Myc protein therapy. Myc protein is implicated with a variety of cancers.Researchers now plan to use their new mice model to further explore the transformation of adenocarcinoma-SCLC, such as detailed research on how the immune system responds to this change normally.
Compilation source: scitechDaily
