Lung cancer remains the leading cause of mortality worldwide, but scientists have emerged a better understanding of the genetic background of the disease, including mutations that contribute to its development. It is known that mutations in the EGFR gene is a particular risk factor for cancer of the lung and the emergence of resistance to other effective therapies, but the mechanism remains unclear.
In the new study, published in the JCI Insight Journal, scientists from Osaka University have identified a protein called semaphorin role at 7a in resistance to the important class of cancer drugs called EGFR-TKI, in mutated cells in adenocarcinoma, the most common form of lung cancer. Their work offers an analysis of the protein to predict patient prognosis and may determine the treatment of the disease.
A team of researchers, based on earlier work showed that the so-called mutation-drivers, which may contribute to cell proliferation or to limit the body's ability to contain drugs or cancerous changes, are a key factor in the treatment. It is known that mutations in the EGFR gene are common in adenocarcinoma of the lung, so the research team looked for other genes that were expressed in connection with the mutation and identified the semaphorin 7a.
"After identifying the high expression of semaphorin 7a in connection with the EGFR mutation in cell-based assays, we confirmed comparable results on clinical samples of human lung adenocarcinoma, - says senior author Atsushi Kumanev -. When we have reduced the expression of semaphorin 7a , they found that the cells become less drug-resistant EGFR-TKI, while the reverse situation occurs when there is overexpression of the protein. "
The command is then examined the mechanism underlying this effect, and discovered that high levels of semaphorin 7a leads to inhibition of apoptosis, a process by which the organism causes death of cells which are abnormal or reached the end of their productive life. The findings suggest that cancer cells can be destroyed when Semaphorin 7a is present at high levels.
"Our work suggests that semaphorin 7a may be useful for the prediction of lung adenocarcinoma, - says Izumi Nagatomo researcher -. With regard to the treatment of this disease, our results may also be useful, as we have shown that the beneficial effects of the treatment can be increased through a combination of EGFR inhibitors and MEK inhibitors in cells resistant to cancer treatment lung. "
The team hopes that their work will improve the fight against lung cancer, enhance the quality of life of patients and potentially lead to increased levels of disease control.