Pancreatic Cancer of The Head and Body/Tail Regions Are Distinct Diseases That May Benefit From Discrete Therapies

To investigate if PHC and PBTC have different overall survival, molecular signature and response to chemotherapy, Maen Abdelrahim, MD, PhD, B Pharm, associate professor of medicine in oncology and director of the Cockrell Center for Advanced Therapeutics at Houston Methodist, performed a retrospective study of patient records from Houston Methodist from July 2016 to June 2020. Abdelrahim looked at 101 patient records and collected information on patient demographics, tumor location, pathology, staging, molecular profiles, treatment history and survival. A comparison of PHC and PBTC did not reveal any statistically significant differences in overall survival, response to chemotherapy or overall tumor mutation numbers. However, there was a statistically significant difference between the mutation frequency of TP53 – the gene encoding the tumor suppressor protein p53. The TP53 mutation frequency was found to be higher in PBTC. Other genes assessed included Kirsten rat sarcoma virus, Suppressor of Mothers against Decapentaplegic, cyclin-dependent kinase inhibitor and genes involved in the cell cycle, mitogen-activated protein kinase and DNA repair pathways. Genetic analysis suggests PHC and PBTC to be distinct tumors. According to whole-genome sequencing and RNA sequencing, pancreatic cancer has four sub-types: classical, squamous, aberrantly differentiated endocrine exocrine and immunogenic. This is yet another mode of classification among pancreatic cancers. Interestingly, PBTC was found to have more squamous subtypes. Similar molecular abnormalities also exist in pancreatic squamous subtypes and lung squamous subtypes such as loss of mutations in several genes, which indicates possibilities of success with similar therapies. Since squamous cell lung cancer is more sensitive to gemcitabine treatment, it is plausible that PBTC is more responsive to gemcitabine-based treatment as well. To advance pancreatic cancer treatment options, future studies to test this hypothesis and to determine whether PHC and PBTC show differential responses to targeted therapy or immunotherapy need to be conducted. According to Abdelrahim, “Even though pancreatic head cancer and pancreatic body/tail cancer have similarly poor overall survival and response to chemotherapy, the different presentations and molecular profiles indicate they are different diseases,” said Abdelrahim. “Utilization of molecular profiling to develop individualized therapies is needed. Pancreatic body/tail cancer has significantly more mutations involved in TP53 mutations and its predictive role in gemcitabine sensitivity should be explored in future studies.”