Absence of anti-tumor protein may be contraindicated in EGFR-targeted therapies

A lack of protein that works to prevent tumor formation may explain why some patients resist common cancer treatment, according to researchers at Penn State College of Medicine. They said testing cancers for the presence of this protein could help clinicians of patients who may have resistance or recurrence when treated with the drug.

Epidermal growth factor receptor (EGFR) is a protein that plays a role in cell division and survival signs and is active in skin, bladder, esophageal, lung, liver, pancreatic, colon, and head and neck cancers. Patients with high levels of this protein in their tumors usually have a poor prognosis. EGFR target therapies are widely used in clinical practice and are often effective at first in many patients. However, some patients are resistant to the treatment and many initially responded to treatment resuscitation within a year.

Douglas Stairs, associate professor of pathology and laboratory medicine and epidemiology, studied why these patients may be resistant to EGFR treatments. He said mutations in the gene containing the instructions to build EGFR or other genetic and cellular factors account for about 70% of immune factors.

There are still reasons for conflict that scientists cite. Our previous work has shown that too much EGFR and lower levels of a protein called p120 catenin (p120ctn) can cause cancer to develop. We hypothesized that reduced levels of p120ctn may also be resistant to EGFR treatments. “

Douglas Stairs, Penn State Cancer Institute Researcher

In healthy cells, p120ctn enhances cell-to-cell communication by interacting with other proteins to strengthen connections between epithelial cells, which are a barrier between the outer and inner surface of the cell. group. According to Stairs, scientists know that cancer cells have often reduced p120ctn levels, but they are not sure why.

To test their hypothesis, stairs and colleagues of esophageal cancer cells underwent genetic engineering – one set with normal doses of EGFR and p120ctn, one set with higher doses of EGFR, one set with lower doses of p120ctn and another set with high levels of EGFR and low amounts of p120ctn. They then treated each cell line with a series of EGFR target treatments.

Cells with high levels of EGFR died when treated with the therapies, while those with normal doses of EGFR were not affected by the treatments. The cell lines containing high levels of EGFR and lower levels of p120ctn were contraindicated – indicating that loss of p120ctn is an essential component of the cell’s resistance to targeted EGFR therapies. The results were published in PLOS AON.

Stairs said that while these results are promising, his lab will continue to investigate the role of p120ctn loss in the fight against EGFR therapy by testing the effect in cancer cells sampled from patients. with colon, lung, oral or other cancers. They will also examine whether the cells with increased EGFR and p120ctn are reduced against other EGFR treatments approved by the U.S. Food and Drug Administration.

“We need to further investigate how the loss of p120ctn causes this,” Stairs said. “For now, we know that if patients with high levels of EGFR in their samples have also been tested for their p120ctn levels, it may give clinicians an idea of ​​what patients at risk for treatments aimed at EGFR or redistribution. . “