New findings by a team of researchers from National Yang Ming University and Taipei Veterans General Hospital have shed light on drug resistance in colorectal cancer.
Colorectal cancer is the most common type of the disease in the nation, with an average of more than 13,000 people diagnosed with that form of cancer every year.
The condition is also the third-leading cause of cancer-related death in the nation, claiming more than 4,000 lives a year.
Patients with stage IV colorectal cancer are treated with targeted therapies, of which epidermal growth factor receptor (EGFR)-targeting therapy is the main strategy.
Responsiveness to the therapy is assessed by screening for a mutated KRAS gene, the presence of which is indicative of resistance to anti-EGFR therapy since it is estimated that more than half of all colorectal cancers manifest in patients whose KRAS gene contains no mutation.
However, about 30 to 40 percent of those who test negative for KRAS mutations and receive EGFR-targeting therapy still go on to develop resistance to the drugs, the research team said.
The researchers said that past studies have shown that malignant colorectal cancer stem cells can exacerbate cancerous tumor growth.
In their research, the team discovered that it is the transcription factor “Snail” in colorectal cancer stem cells, which regulates miroRNA-146a, that directs the tumor-growth-promoting symmetrical cell division of the stem cells. This in turn leads to metastasis and resistance to EGFR inhibitors, the team said.
“If we can repress [the activity of] microRNA-146, the cancer can also be repressed,” said Wang Hsei-wei (王學偉), a professor of microbiology and immunology at National Yang Ming University and a co-author of the study.
“Detecting microRNA can also help determine how serious the cancer and drug resistance afflicting a patient are,” Wang said.
The study’s results were published in leading scientific journal Nature Cell Biology this month.