Taking lung cancer treatment to another level

Lung cancer has long been one of the commonest and deadliest cancers worldwide. Thanks to the CUHK research group and the Asia Thoracic Oncology Research Group led by Professor Tony Mok, the death rate has been going down in recent years. They have decoded the common mutated genes in lung cancer and developed targeted therapies, including immunotherapy, that have successfully increased patients’ lifespans. These innovative therapies redefined global paradigms in lung cancer treatment, providing patients with fresh hope.

The research group led by Professor Mok announces the efficacy of Gefitinib as a targeted inhibitor to control the growth of EGFR cancerous cells.

Leading the research and clinical application of targeted lung cancer therapy

To patients with advanced lung cancer and their doctors, targeted medication was beyond their imagination until about two decades ago. “Apart from chemotherapy, we had no other treatment options if a lung cancer patient could not undergo a surgical operation. But now, almost every patient can receive targeted therapies or immunotherapy after being screened for the mutated genes and biomarkers, which are classified into EGFR mutation, ALK translocation, ROS1, uncommon mutations and PDL1 status. We achieved this by ‘breaking down a boulder’,” said Professor Mok.

For years, Professor Mok and his teams have researched patients with epidermal growth factor receptor (EGFR) mutations. In 2004, Harvard University discovered that this mutation can activate human body cells to divide and grow out of control, forming tumours. This is particularly common among Asians, accounting for about 30% of lung cancer cases. Many of these patients, non-smokers in particular, seldom go for checkups unless obvious symptoms occur. By that time, they are probably in the advanced stage of the disease and on average survive for less than a year. To tackle this issue, a group of Asian scientists led by Professor Mok conducted the IRESSA Pan-Asia Study (IPASS) and announced a major discovery in 2008. “We found a targeted inhibitor that can effectively control the growth of EGFR cancer cells. Patients need only one dose per day and do not need to undergo chemotherapy, which is relatively more toxic. The outcome is better than that of chemotherapy too,” explained Professor Mok.

A ceaseless battle against cancerous mutations

From that time onwards, Professor Mok has made major contributions to research on gene mutations and targeted therapy. Two other common driver oncogene mutations were discovered — anaplastic lymphoma kinase (ALK) translocation and c-Ros oncogene 1 (ROS1) mutation; several generations of targeted therapies have been developed to overcome cancer resistance. Professor Mok added, “A few years ago, we developed a new molecular targeted therapy for lung cancer patients with EGFR mutation whose tumours had acquired resistance to first-line targeted therapy. This new treatment paradigm provides a new line of defence that stops the disease from worsening, meaning patients’ lifespans can be doubled.”

Professor Mok joined CUHK Faculty of Medicine in 1996. As a pioneer in the research on lung cancer, he has defined international standards for treating the disease.

The discovery was ranked by the prestigious The New England Journal of Medicine as one of the most notable research papers of the year. It has also laid the foundation for the development of personalised targeted therapy. In addition to decoding genes, Professor Mok is also heavily engaged in immunotherapy research. He has demonstrated that immunotherapy is an effective treatment for lung cancer patients who have high PD-L1 expression, which release a “brake” on the immune system and stop immune cells from killing certain types of cancer cells. The research findings have been accepted by the U.S. Food and Drug Administration for extensive clinical applications.

Professor Mok’s journey started as a relatively lonely one 20 years ago, when research on lung cancer wasn’t gaining widespread attention. Starting his research from zero, he has now become an internationally renowned expert in lung cancer, earning the title of “Giant of Cancer Care” from leading oncology platform OncLive. He believes that hard work is the key to success, but that an innovative mind is also a necessity in this ever-changing world. “I never thought that I would lead the battle against cancer when I began to practise medicine,” he said. “But I saw opportunities and thought it would be a pity if I just let them go. I want to do my best, no matter how small the change I can make to improve people’s lives.” 

As well as conducting research, Professor Mok also teaches. “I have under my care a lot of research students from CUHK, mainland China and overseas. Besides guiding them through their studies, I also help them to develop soft abilities such as leadership, communication and expression skills. They have to learn how to communicate with patients. Doctors must show respect for life. No matter what your role is, a clinical practitioner or a researcher, patients are always at the centre.”

There is still a long way to travel along the road of fighting cancer. Cancer cells will keep mutating and become drug resistant; medicine that is effective today may become obsolete tomorrow, so new therapies must therefore be developed. Professor Mok said that his future research will focus on the efficacy of different drugs in immunotherapy, the application of antibody-drug conjugates (ADC) on lung cancer, and the development of lung cancer vaccines.

“When I see a patient recovering, I feel rewarded; it is this feeling that drives me on to work harder.”　

— Professor MOK Shu Kam, Tony

Chairman, Department of Clinical Oncology

Li Shu Fan Professor of Clinical Oncology, CUHK

Research areas: Targeted therapy and immunotherapy in lung cancer

Major achievements:

• “Giant of Cancer Care” by OncLive®, a leading multimedia cancer resource (2020)
• Lifetime Achievement Award, European Society for Medical Oncology (2018)
• Fellowship of the American Society of Clinical Oncology, Paul Bunn Jr Scientific Award (2017)
• Named “Highly Cited Researcher” for many years