Lung Cancer

Overview

In China, there are nearly 4.5 million cancer patients and lung cancer is the most common type, accounting for nearly one-third of cancer patients. Nearly 80% of lung cancers are classified as non-small cell lung cancer or NSCLC. The treatment for advanced stages of NSCLC had been limited to cytotoxic chemotherapy. Through cutting-edge molecular-based research, the benefits of personalized medicine are now available for NSCLC patients. Targeted agents – called EGFR TKI – have been developed to target and specifically inhibit EGFR, a cell protein that causes uncontrolled cell growth or cancer, including NSCLC.

The research has shown that specific groups of NSCLC patients such as women, patients who have never smoked or only smoked lightly, and patients of Asian origin have changes in the molecular make-up of EGFR – also called mutations – that allow the tumor to be highly responsive to the targeted therapy, EGFR TKI.

In fact, in 2009, Professor Tony Mok,  his collaborators at The Chinese University of Hong Kong and other prestigious institutions confirmed, in a landmark clinical study, that EGFR TKI is the first-line therapy for NSCLC patients who have these “sensitive mutations”. NSCLC patients from nine countries in East Asia who had EGFR “sensitive mutations” had a better response and experienced much less unpleasant side effects with EFGR TKI than those treated with standard chemotherapy.

Challenges

Unfortunately, all patients who benefit from targeted EGFR TKI therapy will eventually develop resistance to the drug. An unmet clinical need is to learn why this resistance occurs so that a strategy can be developed to give these patients a therapy that will continue to work and effectively fight their cancer. To address this critical problem in personalized medicine, AFCR previously supported Professor Tony Mok at The Chinese University of Hong Kong to investigate why NSCLC patients become resistant to EGFR TKI.

Approach

Prior results from the Mok laboratory as well as other research laboratories had determined that patients may have another mutation in EGFR called “resistant mutation” that may cause their tumor to become resistance to EGFR TKI therapy. Professor Mok reasoned that how an individual patient responds to EGFR TKI may depend on the tumor’s balance between these sensitive mutations – which enhance the tumor’s response to the targeted therapy, and the amount of the resistant mutation – which reduces the tumor’s sensitivity.

Impact

In 2009, Professor Mok had established EGFR TKI as the standard first-line therapy for NSCLC patients whose tumors have the sensitive EGFR mutations. While most of these patients respond to EGFR TKI for a while, eventually, all patients relapse and their tumors begin to grow again. An understanding of how patients develop resistance to this important targeted therapy is key for patients to experience longer disease-free survival and overall survival. This knowledge could help develop a future strategy for the prevention or delay of resistance to EGFR TKI.