Editor’s Note: On October 18-19, 2024, the CACA Integrative Gastric Cancer Conference was held in Wuhan, bringing together multidisciplinary experts from around the world to discuss the latest advances, standards, and research developments in gastric cancer diagnosis and treatment.During the conference, Oncology Frontier interviewed Dr. Xiangdong Cheng, Secretary of Zhejiang Cancer Hospital. Professor Cheng shared insights into the role of the oral-gastric microbiome in gastric cancer and the progress of his research on clinical applications. Based on his extensive clinical experience, Professor Cheng also offered valuable career guidance for young physicians. Here are the highlights of the discussion:

Oncology Frontier: At this conference, you presented on the impact of the oral microbiome on gastric cancer development and shared some recent findings. Could you summarize the key points of your report?

Dr. Xiangdong Cheng: The human intestine is the largest microbial habitat in the body, with the oral cavity following closely. While studies on the gut microbiome are well-established, especially in relation to colorectal cancer and metabolic diseases, research on the microbiome’s role in gastric cancer is still in its infancy. Apart from the well-recognized association of Helicobacter pylori (Hp) with gastric cancer, recent studies have also focused on the influence of oral bacteria that migrate to other parts of the gastrointestinal tract.

The human mouth harbors over 700 bacterial species, carried into the stomach through approximately 1.5 liters of saliva daily. This oral bacteria travels from the stomach to the intestines, eventually being excreted. We believe that, once they migrate to the stomach, some of these bacteria may transform into pathogens. Our research has identified 50-60 bacterial species strongly associated with gastric cancer. Notably, our studies have examined differences in the tongue coating between gastric cancer and non-cancer patients.

In our studies, gastric cancer patients’ tongue coatings differ significantly from those of non-cancer patients. To explore this further, we conducted experiments by introducing mixed saliva and tongue coatings from cancer and non-cancer patients into germ-free mice. Mice receiving samples from cancer patients showed a significantly shortened lifespan and severe gastric inflammation, suggesting a strong link between the oral microbiome and gastric inflammation. This finding prompted us to conduct a series of studies:

1. AI-Driven Tongue Coating Image Analysis: Based on the traditional Chinese medicine perspective that changes in tongue coating indicate health status, we developed an AI-driven model to screen high-risk gastric cancer populations through tongue coating images. We created a portable tongue coating analyzer for clinical testing, which improved the positive tumor screening rate from 1.16% to 2.4%, more than doubling the effectiveness of traditional questionnaires.
2. Multi-Omics Study on Tongue Coating Bacteria: To further increase screening sensitivity, we explored the bacterial profile on the tongue using proteomics, metagenomics, and metabolomics. Notably, our research on metabolomics-based gastric cancer screening using tongue bacteria was accepted by Gastroenterology, marking a global breakthrough in tongue-based gastric cancer diagnosis.
3. Metagenomics and AI-Integrated Screening Model: We combined metagenomic data with AI imaging analysis, raising the positive screening rate to 5.6%. This innovative approach has shown promising results, and we are working on publishing a high-quality research paper.

Our ultimate goal is to bring this model into clinical practice. We plan to conduct a prospective randomized controlled trial comparing this approach with standard clinical methods. If successful, we hope this model will become a standard gastric cancer screening tool in China.

Oncology Frontier: You’ve been deeply involved in translational research on advanced gastric cancer since 2006. Could you share some of the major accomplishments from these years of research?

Dr. Xiangdong Cheng: Gastric cancer is highly prevalent in China, with a significant number of cases presenting at an advanced stage. Around 30-40% of patients are diagnosed at a stage where curative surgery is no longer an option. Historically, these patients relied on medical therapies, with an average survival time of only 10-12 months.

In 2006, we launched a phase II clinical trial using a triple-drug chemotherapy regimen (apatinib, S-1, and paclitaxel) for unresectable advanced gastric cancer patients. Among 72 participants, 50 achieved resectable status after three to four chemotherapy cycles. This cohort’s average survival extended to 30.2 months—an impressive threefold increase compared to standard medical therapy. Over the years, we’ve conducted four clinical studies in this field and accumulated significant experience.

Despite these advancements, advanced gastric cancer remains challenging. Our primary goal is to reduce advanced cases; however, if patients do progress, we aim to provide treatment options that offer them hope for extended survival. In recent years, our team has focused on various metastasis types in advanced gastric cancer, such as liver, ovarian, peritoneal, and lymph node metastasis, identifying multiple critical targets and planning further biological research. Through these combined efforts, we aim to improve conversion success rates and enhance both survival and quality of life for advanced gastric cancer patients.

Oncology Frontier: How do you balance clinical work and research? Do you have any advice for young gastrointestinal oncology doctors?

Dr. Xiangdong Cheng: Having gone through similar stages myself, I can relate to the demands placed on today’s oncology doctors. For a surgeon, proficiency in surgery alone is insufficient; one must also be knowledgeable in medical therapies, radiation therapy, and fundamental scientific principles, all while training students and managing responsibilities. To be a successful doctor, one must develop skills across multiple dimensions.

Our hospital has initiated programs to cultivate multi-skilled clinician-scientists. In each stage, doctors should focus on their primary responsibilities—whether studying as a student, innovating in post-doctoral research, or practicing as a clinician. Our hospital provides newly recruited doctoral graduates the opportunity to enter a post-doctoral research station for two to three years to reinforce their scientific foundation. This training allows many to secure national projects, which greatly benefits their growth.

Finally, I advise young doctors to align their long-term goals with their unique strengths. Each career path is different; some excel in clinical work, while others thrive in research. The need for versatile talent is increasing, so we encourage setting high goals for both short-term and long-term professional plans.

Ultimately, we need a large cohort of clinician-scientists focused on Chinese-specific issues, producing original results that contribute to global medicine.

Dr. Xiangdong Cheng MD, PhD, Professor, and Doctoral Advisor Secretary, Zhejiang Cancer Hospital Deputy Academic Director, Hangzhou Institute of Medical Research, Chinese Academy of Sciences Vice President, Chinese Anti-Cancer Association Director, Zhejiang Provincial Upper Gastrointestinal Cancer Clinical Research Center Chair, Digestive Tract Cancer Prevention and Treatment Key Laboratory of Zhejiang Province