At the recent 7th Tianfu Oncology Conference, Professor Jie Wang from the Cancer Hospital, Chinese Academy of Medical Sciences, delivered a keynote presentation titled “Integrative Strategies in Lung Cancer: Targeted Therapy, Immunotherapy, and ADC Management.”
In her talk, Prof. Wang emphasized that targeted therapies, immunotherapies, and antibody-drug conjugates (ADCs) are the three pillars reshaping the treatment landscape of lung cancer. However, resistance remains a persistent challenge. She proposed that a combinatorial and coordinated approach may offer a promising pathway to overcome therapeutic resistance.
Oncology Frontier had the privilege of interviewing Prof. Wang on-site, where she shared further insights into drug resistance and emerging strategies in anti-cancer treatment.
Integrating Genetic Testing into Clinical Practice: Toward Truly Personalized Lung Cancer Treatment
Oncology Frontier: Immunotherapy resistance remains a major challenge in the clinical management of lung cancer. What strategies do you believe are key to overcoming resistance and improving long-term survival outcomes?
Prof. Jie Wang: Resistance is a persistent issue in the field of cancer treatment. Whether it’s traditional chemotherapy or newer approaches such as targeted therapy, immunotherapy, antibody–drug conjugates (ADCs), bispecific or trispecific antibodies, resistance ultimately emerges. Therefore, during drug development, it is essential not only to study the drug itself but also to explore potential mechanisms of resistance and formulate proactive strategies to counter it.
Take immunotherapy as an example: the tumor immune cycle involves seven key steps, and abnormalities at any of these points can lead to resistance. If, for instance, neoantigen generation is impaired, the immune response may be ineffective from the outset. Similarly, defects in antigen presentation or T-cell recognition can also result in treatment failure.
It is critical that the development of new immunotherapies be accompanied by strategies aimed at overcoming resistance. Combining PD-(L)1 inhibitors with other therapies is one such approach. For example:
- Combining with chemotherapy may enhance neoantigen release, improving immune recognition and reducing resistance risk.
- Combining with anti-angiogenic agents may reverse T-cell exhaustion, normalize tumor vasculature, and improve drug delivery.
- Combining with ADCs can produce synergistic effects through multiple mechanisms, such as promoting positive immune modulation and reducing suppressive immune factors—thereby minimizing resistance.
In my presentation, I discussed an integrative strategy for managing targeted therapies, immunotherapies, and ADCs in lung cancer. For instance, when studying resistance to targeted therapy, one must consider how the tumor microenvironment may contribute to secondary mutations in target pathways. In the context of immunotherapy resistance, clonal evolution within the microenvironment is also a key factor. Furthermore, all three components of ADCs—payload, linker, and antibody—can influence resistance, and strategies should be tailored accordingly to address each aspect.
Looking ahead, while new therapies and combination strategies for overcoming resistance continue to emerge, the core principle remains unchanged: a deep understanding of resistance mechanisms is essential. Only through this understanding can we develop precise and effective solutions to combat resistance in cancer treatment.
Integrating Genetic Testing into Clinical Practice: Toward Truly Personalized Lung Cancer Treatment
Oncology Frontier: With continuous advancements in genetic testing technologies, how do you see these results being better integrated into clinical treatment decisions to realize truly personalized care?
Prof. Jie Wang: For certain subtypes of lung cancer, particularly lung adenocarcinoma, personalized treatment based on molecular subtyping has already become a clinical reality. Approximately 70%–80% of lung adenocarcinomas can now be further stratified—much like slicing a cake—allowing for subtype-specific treatments.
As research progresses, molecular subtyping is becoming increasingly refined. For example, the classification of EGFR-mutant lung cancer has evolved significantly—from the early dichotomy of EGFR-positive vs. EGFR-negative, to now differentiating between common mutations, uncommon mutations, resistance mutations, and EGFR-driven tumors with bypass pathway activation (such as c-MET) or downstream signaling abnormalities (such as PI3K/AKT). Going forward, treatment strategies will need to align with these nuanced classifications, enabling more tailored mono- or combination-targeted therapies to be selected for each patient.
In contrast, immunotherapy subtyping currently faces limitations. Historically, biomarkers like PD-L1 expression and tumor mutation burden (TMB) have been used to predict response, but these approaches fall short in the era of combination immunotherapy, where the predictive value of a single biomarker is often insufficient.
Future efforts must focus on developing more integrative subtyping models that combine multiple dimensions—such as tumor subtype, driver gene status, and the tumor micro- and macro-environment—alongside new tools like big data analytics and artificial intelligence. For instance, while patients with both driver gene mutations and high PD-L1 expression have typically been considered unsuitable for combining TKIs with immunotherapy, more refined subtyping might identify subsets of patients who could actually benefit from such targeted-immunotherapy combinations.
China’s Global Role in Lung Cancer Treatment: Advancing Through Innovation and Collaboration
Oncology Frontier: From a global perspective, how can China enhance its competitiveness in lung cancer treatment through international collaboration?
Prof. Jie Wang: China’s anti-cancer efforts have entered a golden era of development. Supported by national policies, domestic innovation in original drug development is thriving. Pharmaceutical companies, clinicians, and researchers are actively engaging in cross-disciplinary collaboration, propelling China’s oncology landscape—especially in lung cancer, breast cancer, and gastrointestinal cancers—from a stage of catching up and running alongside to leading in certain areas.
To build on this momentum, we must first strengthen internal collaboration—bringing together cutting-edge technologies such as artificial intelligence, and fostering deeper synergy between industry, frontline clinicians, and scientists. At the same time, international academic exchange should be further promoted. We need to actively participate in the activities of globally recognized academic organizations, such as supporting Chinese scholars in seeking election to the International Association for the Study of Lung Cancer (IASLC) Board of Directors, thereby enhancing China’s presence and voice in international oncology forums.
By continuously working together as a national academic and clinical community, we can further improve our external development environment and open up new possibilities for China’s contributions to global cancer treatment. With collective effort, I am confident that we can shape a more prominent and impactful future for China in the fight against cancer.
Professor Jie Wang
Cancer Hospital, Chinese Academy of Medical Sciences
- Director of the Department of Thoracic Oncology, Cancer Hospital, Chinese Academy of Medical Sciences
- Tenured Professor, Peking Union Medical College
- Assistant to the President, Cancer Hospital, Chinese Academy of Medical Sciences
- President, Shanxi Branch of the Cancer Hospital, Chinese Academy of Medical Sciences
- Chief Physician and Doctoral Supervisor
- Recipient of the 2021 Ho Leung Ho Lee Foundation Award for Science and Technology Progress
- Recipient of the National “Outstanding Young Scientist” Fund
- Vice President, Chinese Society of Clinical Oncology (CSCO)
- Chair, Multidisciplinary Committee, Chinese Anti-Cancer Association
- Chair, CSCO Committee on Small Cell Lung Cancer
- Chair, CSCO Committee on Advanced Small Cell Lung Cancer
- Chair, Chinese Anti-Cancer Association Committee on Advanced Small Cell Lung Cancer
- Honored with multiple national-level awards, including First Prize in National Science and Technology Progress (as first completer), Wu Jieping Medical Innovation Award, National Innovation Leadership Award, and the China Young Female Scientist Award
