Editor's Note: Renal cancer is one of the three major malignancies in the urinary system. Early-stage renal cancer often presents with concealed symptoms, making it difficult to differentiate between benign and malignant tumors. Advanced renal cancer primarily relies on targeted or immunotherapy, yet the effectiveness of existing targeted drugs is limited, and resistance tends to develop easily. Therefore, conducting targeted translational research based on clinical problems offers hope for improving the current state of renal cancer diagnosis and treatment in China. At the 8th West China Uro-Oncology Tianfu Academic Conference held in Chengdu, Oncology Frontier invited Dr. Kan Gong from the Institute of Urology at Peking University and the Department of Urology at Peking University First Hospital to share insights into the current state of renal cancer diagnosis and treatment in China, as well as the highlights of his team’s work in translational research.

Oncology Frontier: Recent progress in the renal cancer field has addressed some patient needs. Based on your clinical experience, could you share the current state and characteristics of renal cancer diagnosis and treatment in China?

Dr. Kan Gong: This question covers a broad range of topics and involves multiple aspects.

First, renal cancer is one of the three most common malignancies in the urinary system in China. According to statistics released last year by the Institute of Urology at Peking University, over 1,700 renal cancer surgeries were performed in 2023, marking a historic high. However, about one-third of patients already had metastatic renal cancer at their first outpatient visit, reflecting the current state of renal cancer in China: the proportion of early diagnoses remains suboptimal.

Second, China currently has approximately 500,000 to 700,000 renal cancer patients, with 70,000 to 80,000 new cases diagnosed annually. This enormous patient population places immense pressure on healthcare workers. Particularly for metastatic patients, the five-year survival rate is less than 10%. Furthermore, treatment for metastatic renal cancer relies heavily on imported original targeted drugs, with an efficacy rate of about 20% to 40%. Most patients develop resistance after a period of treatment.

In summary, China’s current renal cancer diagnosis and treatment face several challenges:

1. A large number of late-stage patients.
2. Limited efficacy and easy resistance to existing drugs.
3. Over 70% of patients experience recurrence or metastasis, resulting in an overall five-year survival rate of less than 10%.

Additionally, as precision medicine becomes a global trend in healthcare, achieving more precise imaging-based diagnosis, accurate molecular subtyping, and individualized treatment strategies based on molecular characteristics has become an urgent issue to address.

Oncology Frontier: Clinical trials can provide more evidence-based data for clinical decisions and selecting the optimal beneficiary populations. How do you think clinicians can better integrate research into their practice?

Dr. Kan Gong: Effectively conducting clinical trials is key to addressing real-world clinical challenges and guiding clinicians in their professional growth. By identifying issues in clinical practice and using them as the foundation for designing clinical trials, we can  ensure these problems are systematically resolved.

During this process, it is crucial to identify pressing challenges and key focus areas. Through scientifically rigorous and forward-looking designs, particularly by employing multicenter, large-sample, randomized controlled trials (RCTs) and long-term follow-up studies, we can generate high-quality evidence to guide clinical practice.

Such robust evidence not only helps update existing guidelines and consensus, but also provides new directions and foundations for future research. Ultimately, every clinical trial should aim to address specific clinical challenges. By identifying these core issues and conducting targeted research, the resulting studies will be meaningful and impactful.

Oncology Frontier: What progress has your team made in translational research on renal cancer, and how might these findings impact clinical practice in China?

Dr. Kan Gong: As previously mentioned, renal cancer in China faces significant challenges. Over the past two decades, our team has deeply explored key areas such as the mechanisms of renal cancer development, molecular subtyping, and the development of molecularly targeted drugs. This long-term, dedicated exploration has provided us with extensive scientific knowledge and practical experience.

Based on over 20 years of solid research, our efforts are now yielding results. The academic value and application potential of our findings are becoming increasingly evident. Here, I will briefly highlight some of our key work:

Imaging Diagnosis

Accurate diagnosis is critical for developing effective treatment plans for renal cancer. Due to the lack of specific symptoms and signs in early-stage disease, imaging examinations remain the most commonly used diagnostic tool in clinical practice. For the most prevalent type of renal cell carcinoma—clear cell renal cell carcinoma (ccRCC), which accounts for over 75% of all renal cancer cases—traditional methods such as CT and MRI are primarily relied upon for initial assessment. However, their diagnostic accuracy is no higher than 50%. Additionally, about 15% of patients require biopsy to obtain further information, a procedure that carries potential risks such as bleeding, needle tract seeding, and other complications.

Currently, the use of  18F-FDG PET/CT for ccRCC yields a specificity of only 48%–52%, far below the desired standard. This underscores the urgent need for a novel, non-invasive diagnostic technology specific to ccRCC.

One research focus is the development of molecular diagnostic technologies targeting membrane proteins uniquely expressed in ccRCC. The inactivation of the VHL gene in ccRCC leads to the activation of the HIF pathway, which promotes the expression of downstream proteins. Among these, carbonic anhydrase IX (CAIX), a transmembrane glycoprotein, has emerged as an ideal target for molecular imaging. Studies have shown that PET/CT scans using radiolabeled humanized monoclonal antibodies against CAIX can improve diagnostic accuracy. However, due to the large molecular size of antibodies, challenges such as immunotoxicity, high background signal intensity, and a long in vivo half-life (approximately one week) limit its practical application. Current reports indicate an accuracy rate of about 70%–80% with this approach.

To overcome these limitations, our team collaborated for over two years to develop a novel small-molecule ligand for CAIX, named C1. By optimizing the compound structure and coupling it with short half-life radionuclides, we significantly reduced its metabolic time in vivo to approximately 68 minutes and increased diagnostic accuracy from around 40% with conventional PET/CT to approximately 90%. This project has been granted a national patent and has entered clinical trial stages. We hope to see promising results soon, providing a more efficient and accurate molecular imaging diagnostic tool for ccRCC patients.

Molecular Diagnostics

Since the concept of “precision medicine” was introduced, it has garnered widespread attention in the medical community. However, compared to cancers such as prostate, breast, colorectal, and lung cancer, renal cell carcinoma (RCC) lacks well-defined and widely recognized biomarkers. Factors for early diagnosis or prognosis assessment remain under investigation.

Research has revealed a close relationship between RCC and multigene variations as well as complex signaling pathways, with the VHL-HIF signaling axis identified as one of the most critical mechanisms. This discovery earned the 2019 Nobel Prize in Physiology or Medicine.

Our research team has been dedicated to this field for many years, progressing from following international developments to achieving global leadership in some areas. Based on our understanding of RCC, we selected a representative hereditary renal cancer as a breakthrough point. This monogenic hereditary disease has allowed us to delve deeper into the molecular mechanisms behind the disease. Initially, we designed primers for PCR amplification based on foreign literature to perform genetic testing. Over time, we encountered cases where patients exhibited typical clinical symptoms, but lacked detectable mutations in genetic tests. This prompted us to establish the largest hereditary renal cancer sample database in Asia and the second largest worldwide.

By analyzing a vast number of Chinese patient samples, we identified unique mutation patterns in specific populations, leading to the development of a novel high-throughput diagnostic approach. This innovation has received national patent certification and been successfully translated into clinical applications. The diagnostic method enables the simultaneous screening of 14 different types of hereditary renal cancers, providing critical insights for selecting individualized treatment plans. In the future, as this system is further refined, it is expected to be widely applied to the entire RCC field.

Molecular Subtyping

Through genetic diagnostics, we recognized that different gene mutations correspond to distinct clinical phenotypes and prognoses. Based on this understanding, we developed a novel molecular subtyping method. Compared to traditional methods, this new approach significantly enhances the ability to predict tumor risks in multiple organs, improves overall survival rates, and increases the accuracy of molecular subtyping.

This innovative subtyping strategy has gained broad recognition in the international academic community. Renowned experts in the field of RCC from the National Institutes of Health (NIH) have highly praised the method, considering it a new milestone in precision treatment of RCC and a significant advance in genetic counseling. European researchers have successfully applied this model to predict risks in hereditary RCC, and the method has also shown potential for broader application in other hereditary diseases. Our molecular subtyping and prognosis evaluation model has earned unanimous acclaim wordwide.

AI-Assisted Diagnosis

After two years of collaborative research with with high-tech enterprises, our team has developed an AI-assisted diagnostic system specifically designed for RCC. This system provides instant mobile-based query services for rare hereditary RCC cases, guiding patients to appropriate healthcare institutions and specialists. By streamlining the diagnostic process, it reduces unnecessary expenses and travel, shortens diagnosis and treatment timelines, and achieves precision care and treatment.

Development of Novel Molecular Targeted Drugs

In the field of translational medicine, another significant contribution of our team is the development of innovative treatment strategies, particularly novel molecular targeted drugs. We identified a new target independent of the Nobel Prize-related “VHL-HIF” signaling pathway, collaborating with our partners. Currently, we are developing inhibitors targeting this pathway. These inhibitors have demonstrated initial activity in both in vitro and in vivo studies, and we aim to advance them rapidly to preclinical validation stages to assess their potential in RCC treatment.

HIF-2α as a Therapeutic Target

In 2005, our team proposed at a national oncology conference that, compared to Western populations, HIF-2α is more widely distributed and expressed at higher levels in Chinese RCC patients. Based on this finding, we suggested that HIF-2α inhibitors could represent a novel therapeutic strategy for RCC.

In recent years, international pharmaceutical companies have successfully developed HIF-2α inhibitors, such as Merck’s Belzutifan. Additionally, two domestic pharmaceutical companies in China have also developed proprietary HIF-2α inhibitors. Globally, seven clinical trials investigating HIF-2α inhibitors for RCC treatment are currently underway, and I am honored to serve as the principal investigator for three of these trials in China. Through these translational studies, we hope to obtain compelling positive results and deliver meaningful clinical benefits to RCC patients.

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Dr. Kan Gong

• Deputy Director, Institute of Urology, Peking University
• Deputy Director, Oncology Translational Center, Peking University First Hospital
• Director, Department of Scientific Research, Peking University First Hospital
• Vice Chair, Urology Branch, Chinese Medical Association
• Member, Urological Oncology Group, Chinese Medical Association
• Recipient of the National High-Level Talent Special Support Program (Ten Thousand Talents Program)
• Recognized as “Mid-Young Technological Innovation Leader” by the Ministry of Science and Technology
• Honored as “New Century Excellent Talent” by the Ministry of Education