From left to right, they are Yang Xia, Tony Mok, Wenhua Liang, and Yongchang Zhang.

As lung cancer diagnosis and treatment enter an era of precision and personalization, Chinese researchers are playing an increasingly pivotal role on the international stage through innovation and collaboration. In this special edition of the Mok Talk interview series, hosted by the talented Professor Yang Xia of The Second Affiliated Hospital of Zhejiang University School of Medicine, we are honored to present a conversation with world-renowned lung cancer expert Professor Tony Mok from The Chinese University of Hong Kong. Joining him are prominent early-career scholars such as Professor Wenhua Liang (The First Affiliated Hospital of Guangzhou Medical University) and Professor Yongchang Zhang (Hunan Cancer Hospital). Together, they discuss academic growth, clinical trial design, and the global impact of Chinese innovations—offering a meaningful intergenerational exchange of ideas.

1. Research Journey and Academic Leadership

Yang Xia: Looking back at your research career, what were the key factors behind your major breakthroughs?

Tony Mok: Honestly, I’d say the biggest factor was luck. When I returned to Hong Kong, lung cancer research was gaining momentum, and clinical trials in China were just starting to take shape. I was fortunate to collaborate with leading mainland colleagues like Professors Yilong Wu, Shun Lu, Li Zhang, and Caicun Zhou. Resources were limited back then, and we had little experience—but having the chance to build something together from the ground up was a blessing.

Hong Kong’s unique position, bridging East and West, also gave me an advantage in accessing international resources. The 2004 discovery of EGFR mutations completely changed how we understand lung cancer. In that sense, I believe the key to success is being part of the right moment and seizing opportunities for academic collaboration.

Yang Xia: You credit friends and timing, but your leadership clearly played a vital role. Can you share some practical insights on leadership?

Tony Mok: Leadership comes down to two key qualities: foresight and critical thinking. As a leader, you must anticipate future trends, but also be willing to question the status quo to ensure you’re on the right path.

Take the IPASS study, for example. It was originally designed for all patients, which led to gefitinib being withdrawn in the West. We challenged conventional thinking and focused on non-smokers, Asian patients, and adenocarcinomas—targeting EGFR-mutated populations—which ultimately demonstrated the benefit of TKI therapy.

Yongchang Zhang: For young researchers, challenging pharmaceutical companies or senior investigators can be daunting. What’s your take?

Tony Mok: I’d like to hear your perspective. Many pharma companies in China now propose their own trial designs. If you see issues, how do you handle them?

Yongchang Zhang: Your experience is very enlightening. We must avoid blind acceptance and critically evaluate the scientific rationale behind trial designs. Sometimes, commercial interests may skew results. It’s essential that our designs are scientifically sound and not just commercially appealing.

Tony Mok: I completely agree.

2. Designing and Implementing Targeted Adjuvant Therapies

Tony Mok: Let’s say we’re designing an adjuvant study for ensartinib, a Chinese ALK inhibitor. Can it truly answer the question: is chemotherapy necessary after surgery?

Yongchang Zhang: We could explore creative designs to address gaps left by the ALINA trial.

Yang Xia: We also need to consider patient adherence. Studies like CTONG1104 show that few patients actually complete 2–3 years of adjuvant therapy. So trial design should account for treatment duration, adherence, and safety.

Wenhua Liang: I’d like to share an idea inspired by Professor Mok—about adjuvant use of ensartinib. We’re currently conducting a study with the following features:

First, it targets Stage I lung cancer patients. While adjuvant therapy is well-established in Stages II and III, there’s no consensus for Stage I, especially IA. Even for IB, only EGFR-mutated patients have options, and none exist for ALK-mutant patients.

The reason is likely a failure to enrich for high-risk subgroups, which dilutes outcomes. But now we can stratify by histological features like micropapillary patterns, solid components, STAS, or vascular invasion—as well as clinical high-risk factors. We’ve even developed molecular prediction models.

While MRD positivity in Stage I is low due to detection limits, that doesn’t mean recurrence won’t happen. Enriching for high-risk patients helps establish the value of adjuvant therapy.

Second, the treatment duration is just one year. Data suggest that early-stage patients might benefit from shorter treatment to eliminate minimal residual disease. Extending therapy to 3–5 years doesn’t necessarily improve outcomes.

Professor Yilong Wu has proposed a strategy: reintroduce treatment only upon MRD positivity or signs of recurrence, rather than maintaining long-term therapy—especially since many early-stage patients consider themselves “cured” after surgery and resist extended treatment. Our study aims to improve adherence and cost-effectiveness by limiting treatment to one year.

Tony Mok: What’s the primary endpoint?

Wenhua Liang: We’re using a placebo-controlled design with DFS as the primary endpoint, targeting 200 patients total. We estimate different hazard ratios by genotype and use a umbrella trial design, modeled after ADAURA.

Tony Mok: Very thoughtful. But keep in mind ADAURA focused mainly on Stage II/III. We must be cautious when extrapolating to Stage I.

Wenhua Liang: Absolutely. Our study specifically focuses on high-risk Stage I patients, who differ from average Stage I cases in prognosis.

3. Exploring Strategies for Uncommon Mutations

Yang Xia: Ensartinib is approved for advanced ALK+ NSCLC, initially post-crizotinib, and now in first-line. Our team also explored using it for MET exon 14 skipping mutations, which was quite innovative.

Tony Mok: What led you to try ensartinib in METex14 patients?

Yang Xia: We treated a patient with METex14 mutation who had progressed on crizotinib. Ensartinib, a type 1A MET inhibitor, showed remarkable efficacy. This led to the EMBRACE trial, a Phase II single-arm study enrolling 31 previously treated advanced NSCLC patients. The results were published in eClinicalMedicine:

• ORR: 53.3%
• DCR: >80%
• Median PFS: 6 months
• DoR: 7.9 months

Tony Mok: This is the first study using an ALK inhibitor for METex14, opening a new pathway. How would you assess its value?

Yongchang Zhang: Scientifically, it’s reasonable. ALK inhibitors can have multi-target effects. At the time, selective MET inhibitors like savolitinib were not widely available, so ensartinib filled a clinical need and highlighted its multi-target potential. However, in today’s precision era, we must clearly define whether a new approach is “me-too” or truly “me-better.”

Yang Xia: What are your thoughts on using small molecule targeted therapies or immunotherapy as adjuvant treatments for rare mutations like EGFR exon 20 insertions or KRAS G12C?

Tony Mok: There are challenges. First, clinical trials like LIBRETTO for RET require massive investments. Second, toxicity—MET inhibitors can cause edema or liver issues, which are difficult to manage long-term. Third, cost—without robust data, recommending expensive, prolonged therapy is hard to justify.

For adjuvant immunotherapy, PD-L1 levels are key. In patients with high PD-L1 expression, I may consider it.

4. Academic Growth and Research Strategy

Yongchang Zhang: With increasing competition, how can young researchers find unique directions?

Tony Mok: Stay curious and think independently. Ask yourself: is this a question truly worth exploring? Seek mentors and collaborators, and don’t blindly follow authority. Also, learn to protect your ideas—balance teamwork with integrity and confidentiality.

Yongchang Zhang: How do you balance clinical and translational research?

Tony Mok: Match your team’s strengths with resources. Use existing tools and collaborate wisely to optimize your study design.

Wenhua Liang: One lesson I learned: every study should focus on one core question. Initially, we explored ctDNA as a screening tool in the general population. Professor Mok advised us to focus on high-risk groups instead, to maintain scientific validity. Studying low-risk populations would have expanded the scope blindly and diluted the outcomes.

Also, research must follow strict trial protocols. Even if p < 0.01, if the analysis doesn’t meet pre-defined criteria, it may still be invalid.

Tony Mok: Exactly. Trial design must address the concerns of patients, pharma, and regulators to ensure relevance and feasibility.

Yang Xia: What lessons from your career could help young researchers avoid pitfalls?

Tony Mok: The academic path is full of challenges. Luck matters, but independent thinking and healthy, ethical collaboration are far more important. Always keep patient benefit at the center of your work.

Yongchang Zhang: Should we lower our expectations or keep striving for high-impact work?

Tony Mok: The true value of research lies not in the impact factor but in its real-world clinical contribution.

5. AI in Lung Cancer Research

Yang Xia: DeepSeek and similar tools are gaining attention. How do you see AI’s role in medicine?

Tony Mok: AI has already made a real difference. In clinical practice, voice recognition helps with documentation; CT image analysis supports diagnosis—though legal issues remain. In trials, AI can simulate control arms. In writing, it helps with data processing and drafting—but always needs human review. Ultimately, AI might even become part of the care team.

As the Mok Talk interview concluded, all participants expressed a shared commitment to academic mentorship and collaboration. Professor Tony Mok encouraged young physicians to seize opportunities, raise their voices on the global stage, and pursue innovation with courage and integrity to advance the future of medicine.

Professor Tony Mok
Fellow of the Hong Kong Academy of Sciences  
Chair, Department of Oncology, Faculty of Medicine, The Chinese University of Hong Kong  
Former President, International Association for the Study of Lung Cancer (IASLC)  

Professor Tony Mok has authored over 260 publications in prestigious journals including The New England Journal of Medicine, Science, The Lancet, Nature Medicine, and Journal of Clinical Oncology.  

Honors and Awards:

• Bonnie J. Addario Award (2015)
• IASLC Scientific Award (2017)
• National Science and Technology Progress Award of China (2017)
• CSCO Annual Achievement Award (2017)
• ESMO Lifetime Achievement Award (2018)
• 6th Kobayashi Foundation Award
• Outstanding Leadership Award (2020)

In 2020, he was recognized as an “Oncology Giant” by one of the world’s leading oncology multimedia platforms.

Professor Yang Xia, M.D., Ph.D.
Associate Chief Physician, Associate Professor, Doctoral Supervisor
Vice Chair, Department of Pulmonary and Critical Care Medicine
The Second Affiliated Hospital, Zhejiang University School of Medicine

Honors and Recognition:

• National Science Fund for Excellent Young Scholars (National Excellent Youth Program)
• Recognized as an Outstanding Young and Middle-aged Pulmonologist in China

Academic and Professional Affiliations:

Member, Respiratory Branch, Zhejiang Medical Association

Youth Committee Member, Respiratory Physician Branch, Chinese Medical Doctor Association

Secretary, Interventional Pulmonology Group, Respiratory Branch, Chinese Medical Association

Member, Clinical Science Committee, International Association for the Study of Lung Cancer (IASLC)

Member, Youth Expert Committee, Chinese Society of Clinical Oncology (CSCO)

Professor Wenhua Liang
Chief Physician, Doctoral Supervisor
Director, Thoracic Oncology Department, The First Affiliated Hospital of Guangzhou Medical University
Vice President, Hengqin Hospital
Assistant Director, Guangzhou Institute of Respiratory Health
Director, Office of the National Center for Respiratory Medicine

Academic and Professional Roles:

• Deputy Head, Lung Cancer Group, State Key Laboratory of Respiratory Disease
• Chair, Immunotherapy Committee, Guangdong Thoracic Disease Society
• Vice Chair, Committee of Precision Medicine and Molecular Diagnostics, Guangdong Medical Association

Professor Yongchang Zhang, M.D., Ph.D.
Chief Physician, Professor, Doctoral Supervisor
Director, Early-Phase Clinical Research Center
Deputy Director, Department of Pulmonary and Gastrointestinal Oncology
Hunan Cancer Hospital

Director, Hunan Provincial Engineering Research Center for Lung Cancer Drug Development

Honors and Recognitions:

• National Science Fund for Excellent Young Scholars (Oncology, 2022)
• First Prize, Hunan Provincial Science and Technology Progress Award (First Author)
• Recipient of the “Bethune Medal” of Hunan Province
• Leading Talent in Scientific and Technological Innovation, Hunan Province
• Youth Science and Technology Award, Chinese Medical Association (First Author)