Gastric cancer, a leading cause of cancer-related deaths worldwide, often spreads to the peritoneum, the lining of the abdominal cavity. A team of Singaporean clinicians and scientists have made a significant breakthrough in understanding the mechanisms behind this spread and have demonstrated the potential of a novel treatment approach. The research, published in Gastroenterology and ESMO Open, offers new hope for patients with gastric cancer peritoneal metastases (GCPM), a condition associated with poor prognosis.
Unraveling the Tumor Microenvironment
The research team, from institutions including the National University Hospital (NUH), the National University Cancer Institute, Singapore (NCIS), and Duke-NUS Medical School, employed genomic and transcriptomic technologies to analyze patient samples. This in-depth analysis revealed specific genetic alterations and characteristics within the tumor microenvironment (TME) that contribute to the metastasis of gastric cancer to the peritoneum.
"Our research has pulled back the curtain on the complex biological processes that drive the spread of gastric cancer to the peritoneum," said Dr. Raghav Sundar, Senior Consultant at NCIS and Associate Professor at NUS Medicine. "These findings provide a crucial roadmap for developing more effective and targeted treatments for this devastating disease."
The study highlighted the crucial role of the TME in supporting the establishment and growth of peritoneal metastases. By identifying these mechanisms, the researchers have opened avenues for developing innovative therapies that target the TME, potentially disrupting the cancer's ability to thrive in the peritoneum. They also identified potential biomarkers that could predict the risk of peritoneal metastasis, enabling earlier detection and intervention, and uncovered novel therapeutic targets for GCPM.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, noted, "Prior to our study, there was limited understanding of the tumor microenvironment that contributes to the spread of gastric cancer to the peritoneum... Our results highlight the complexity of gastric cancer metastases, revealing that gastric tumors can use distinct genetic and molecular mechanisms to spread to different organs."
PIANO Trial: A Promising Combination Therapy
In a parallel development, the research team conducted the Phase I PIANO trial, which evaluated the safety and potential efficacy of a novel treatment approach for GCPM. The trial combined Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC), a minimally invasive surgical technique that delivers chemotherapy directly to the peritoneal cavity, with systemic immunotherapy.
The PIANO trial demonstrated that the combination therapy was well-tolerated by patients and resulted in a reduction in tumor burden for some. Molecular profiling of tumor samples revealed an increase in T-cell infiltration, indicating a positive immune response against the cancer.
Professor Jimmy So, Senior Consultant at NUH, who led the PIANO trial, stated, "The PIANO trial results are incredibly encouraging, demonstrating the potential of combining targeted therapy like PIPAC with immunotherapy to improve outcomes for patients... This approach could revolutionize the treatment landscape for this challenging condition."
Implications for Future Treatment Strategies
The combined research efforts represent a significant advancement in the fight against GCPM. The identification of predictive biomarkers and therapeutic targets could lead to personalized treatment strategies, tailoring treatments to the unique molecular profile of each patient's tumor. The success of the PIANO trial suggests that combination therapies leveraging the power of the immune system could offer new hope for patients with peritoneal metastases.
Associate Professor Johnny Ong, Senior Consultant at Singapore General Hospital and NCCS, emphasized the collaborative nature of the research, stating, "Combining bench and bedside research, we have shed new light on the biology of gastric cancer which will pave the way for the much-needed therapeutics in patients with peritoneal metastases."
