Professor Tony Mok
The Chinese University of Hong Kong
Results from Professor Tony Mok and his research team are offering new insights into the mystery of how Asian patients with non-small cell lung cancer develop resistance to targeted therapies.
Professor Tony Mok
The Chinese University of Hong Kong
Personalized Medicine For Non-Small Cell Lung Cancer Patients
Background
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, Professor Tony Mok and his collaborators at The Chinese University of Hong Kong recently 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. The need of the hour 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 is supporting Professor Tony Mok at The Chinese University of Hong Kong to investigate why NSCLC patients become resistant to EGFR TKI.
Solution
Results from the Mok laboratory as well as other research laboratories have 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 reasons that how an individual patient respond 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.
In Professor Mok's new clinical study, Asian non-smoking NSCLC patients, prior to beginning treatment with EGFR TKI, will have their whole resected tumor tissue analyzed for the presence of both the sensitive and resistant mutations. Rather than searching for the resistant mutation in a tiny area of a small sample of biopsy tissue, this method will ensure that even a small quantity of resistant mutation can be identified. The results from this cutting-edge research analysis could help form a future strategy that will prevent or delay the resistance to EGFR TKI.
Impact for Patients
Professor Mok has 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. The results of this much-needed project could help develop a future strategy for the prevention or delay of resistance to EGFR TKI.
