Researchers with the Lockwood Lab at BC Cancer examined why certain lung tumours manage to resist treatment over time, and what can be done to reduce resistance. The study, published in Oncogene, investigates why some patients with lung adenocarcinoma develop a resistance to EGFR inhibitors, a common treatment for this type of non-small cell lung cancer.
Lung cancer is the leading cause of cancer-related death in the world, and about 15 percent of lung cancer patients develop a resistance to EGFR inhibitors – representing hundreds of thousands of patients each year.
“An EGFR mutation is one of the most prominent changes that occur in lung cancer patients, especially those who don't smoke,” said Dr. William Lockwood, distinguished scientist at BC Cancer. “These patients typically respond well to EGFR-targeted therapies initially, but over time they develop a resistance, then recurrence and will eventually succumb to the disease.”
His team is studying how this resistance can be reduced so treatment can work for a longer period of time, ultimately improving survival for these lung cancer patients.
“Over time, the residual cancer cells that survived long-term treatment will become resistant to EGFR inhibitors and will be able to grow again, causing the cancer to recur in patients,” said Rocky Shi, a graduate student in the Lockwood Lab. “We were able to model this progression towards resistance in cell lines grown in the lab, which similarly showed a small population of lung cancer cells that were able to survive and tolerate EGFR inhibitor treatment.”
Using lung cancer cell lines, Rocky identified a mechanism which lung cancer cells use to survive EGFR inhibitors – a protein called integrin-linked kinase (ILK) that was upregulated, or produced more, in these tolerant cells. ILK was shown to play a crucial role in helping lung cancer cells survive and become resistant to treatment.
“In our model, we saw that suppression of this survival mechanism is able to improve response to EGFR inhibitors and delay the onset of resistance. We hope our findings will be translatable to the clinic and can improve outcomes for patients in the future,” he added.
Targeting ILK may offer a new strategy to overcome resistance and improve outcomes for patients with lung adenocarcinoma. Future steps include developing better ILK inhibitors to potentially be used in clinical trials.