Pancreatic Cancer: Genetic Subtype Insights, Therapy Impact
Pat Gulhati, MD, PhD, discusses findings from a comprehensive analysis of genetic, immunological, and signaling pathway variations in pancreatic cancer.
Pancreatic cancer remains a challenge in oncology, but recent research has highlighted the distinct characteristics of its subtypes, offering potential avenues for more targeted therapies. Specifically, a study presented at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium shed light on the differences between pancreatic ductal adenocarcinoma (PDAC), pancreatic adenosquamous carcinoma (PASC), and pancreatic squamous cell carcinoma (PSCC).
Researchers, including Pat Gulhati, MD, PhD, assistant professor at the Rutgers Robert Wood Johnson Medical School, conducted a comprehensive analysis of the genetic, immunological, and signaling pathway variations among these subtypes. Their findings revealed that PASC exhibits unique genetic alterations compared with PDAC. Notably, PASC displayed higher mutation rates in genes such as CDKN1B, SF3B1, PTEN, and BCL9, as well as amplifications in AKT2 and ROS1 fusions.
According to Gulhati, one of the most significant observations was the distinct immunological landscape of PASC. The subtype showed increased expression of PD-L1 and immune-related genes, suggesting a potential for immunotherapy. Additionally, PASC exhibited a higher infiltration of CD4-positive T cells and an elevated interferon gamma signature, indicating a more active immune response compared to PDAC.
In terms of signaling pathways, the YAP pathway demonstrated differential expression in PASC, opening possibilities for targeted therapies currently under development. While overall survival rates between PASC and PDAC were comparable, patients with PASC displayed better prognoses than those with PSCC.
Gulhati, in an interview, emphasizes the importance of next-generation sequencing for all patients with pancreatic cancer, regardless of subtype, to identify personalized treatment options. He also underscored the necessity of germline testing. "It is important to do next-generation sequencing in every single pancreatic cancer patient... because this is how we find new and personalized ways to treat their cancer other than chemotherapy. It is also important to do germline testing in all pancreatic cancer patients," he states.
However, Gulhati cautioned that the chemotherapy protocols remain unchanged based on these preliminary findings. "From a chemotherapy standpoint, we do not have any key takeaways from this study yet. The data are preliminary, and we are looking at a larger cohort of patients with this disease, to validate our findings," he explains.
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