Peritoneal metastases arise from gastrointestinal and gynecologic malignancies, leading to debilitating symptoms and poor prognoses. They remain one of the most challenging manifestations of advanced malignancies, often leading to significant morbidity and limited treatment options.
There are several challenges in improving outcomes of patients with peritoneal metastases, including limited understanding of tumor biology, animal tumor models that do not recapitulate disease and lack of predictive biomarkers. My research has sought to make advances in each of these domains.
Teasing out tumor biology
My lab has focused our tumor biology efforts on appendiceal neoplasms, which are rare, with zero FDA-approved therapeutics. A fundamental barrier to therapeutic advancement is the lack of a deeper molecular knowledge of the phenotypic diversity of cancer and non-cancer cell populations across a spectrum of histologic subtypes.
This is the most comprehensive in-depth study of appendiceal cancer neoplasms that considers the different histologic subtypes. We believe these findings will have an immediate impact on therapeutic development for this rare cancer.
We utilized comprehensive single-cell RNA sequencing to characterize the cell types and molecular mechanisms underlying cellular remodeling in epithelial appendiceal neoplasms.
Analyzing the transcriptome of 126,998 cells from peritoneal metastases samples and healthy controls, we identified 33 distinct cell types/cell states, seven being cancer specific. Among other findings, we identified unique changes in the tumor immune microenvironment and reported the presence of effector immune cells infiltrated with tumor cells.
This is the most comprehensive in-depth study of appendiceal cancer neoplasms that considers the different histologic subtypes. We believe these findings will have an immediate impact on therapeutic development for this rare cancer.
Seeking ways to diagnose earlier
We are also looking for novel biomarkers and other diagnostics for peritoneal metastases, as they are notoriously difficult to detect on modern cross-sectional imaging as well as currently available circulating tumor DNA tests. While surgical visualization is the gold-standard of estimating the burden of cancer, it is challenging to distinguish peritoneal sclerosis or completely treated tumor from untreated viable tumor.
With funding from the National Science Foundation, I am collaborating with scientists at other institutions to develop a multi-modal (computer vision/AI, ultrasound, and Raman spectroscopy) robot to diagnose and annotate intra-abdominal tumors during surgery. The development of this robot will significantly advance our ability to prognosticate peritoneal metastases and make intra-operative therapeutic decisions.
PIPAC: A novel approach to peritoneal metastases
Traditional intraperitoneal chemotherapy has demonstrated limited efficacy due to inconsistent drug distribution. One promising innovation is Pressurized Intraperitoneal Aerosol Chemotherapy, a minimally invasive method for delivering regional therapy to peritoneal tumors. PIPAC seeks to overcome these challenges by utilizing aerosolized chemotherapy under pressure, allowing for uniform drug dispersion and deeper tumor penetration.
At City of Hope, we are leading efforts to evaluate PIPAC through well-structured clinical trials, ensuring that this technique is validated through robust scientific inquiry before broad implementation.
Looking ahead: The future of peritoneal oncology
The future of peritoneal oncology lies in personalized regional therapy, molecularly guided interventions, and innovative clinical trial designs. As we develop next-generation strategies, including the potential for targeted and immune-based therapies, we must remain committed to evidence-driven implementation. Ensuring equitable access to leading-edge treatments through policy reform and institutional outreach will be just as critical as the scientific advancements themselves.
As surgical oncologists, our mission is not just to operate but to innovate—pushing the boundaries of what is possible to improve patient outcomes. The intersection of surgery, research, and policy presents a powerful avenue for transformation in cancer care.
Listen to Dr. Raoof on City of Hope’s new podcast, “On the Edge of Breakthrough: Voices of Cancer Research.” Available on Spotify, Apple Podcasts and at cityofhope.org/edge-of-breakthrough.
City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the U.S. with its National Medical Center named top 5 in the nation for cancer by U.S. News & World Report. To learn more about City of Hope, visit: www.cityofhope.org.
