*August 2020*

Research into mutations in the gene encoding the epidermal growth factor receptor (EGFR) protein has revolutionized non–small cell lung cancer (NSCLC) treatment in recent years, yet the science supporting targeting of this oncogene is still being elucidated.

“It’s such a natural part of management for advanced lung cancer now,” Stephen Liu, MD, associate professor of medicine, director of thoracic oncology, and director of developmental therapeutics at the Lombardi Comprehensive Cancer Center of Georgetown University, in Washington, DC, said in an interview with Targeted Therapies in Oncology. “It’s easy to forget it wasn’t that long ago that we didn’t really understand how these alterations impacted the treatment of cancer.”

Ever since EGFR overexpression on the surface of malignant cells was first identified in patients with lung cancer, investigators have been working to determine how best to leverage that insight. “We saw that if you had one of these mutations within EGFR, your tumor was exquisitely sensitive to these EGFR kinase inhibitors,” Liu said.

That realization prompted a wave of new research, including a meta-analysis showing that about one-third of patients with NSCLC harbor an EGFR mutation.1 Insights into the molecular underpinnings of NSCLC can help identify subsets of patients who have different prognoses and are likely to benefit from specific types of treatment. Over the past several years, investigators have capitalized on this expanding knowledge base to foster dramatic results, but they are also chasing a moving target. Resistance to earlier tyrosine kinase inhibitors (TKIs) is growing, and the molecular heterogeneity of NSCLC is prompting investigators to explore a wide range of treatment combinations and strategies to more precisely tailor treatments to individual patients. Read more.