Is oncolytic adenoviral-mediated immunotherapy through p53-overexpression the solution to refractory pancreatic ductal adenocarcinoma?

Evaluation of: Araki H, Tazawa H, Kanaya N, et al. Oncolytic virus-mediated p53 overexpression promotes immunogenic cell death and efficacy of PD-1 blockade in pancreatic cancer. Mol Ther Oncolytics. 2022;27:3-13.Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis. PDAC has a dense, desmoplastic stroma and immunosuppressive microenvironment, which impedes current treatment options. Immunotherapy delivered via oncolytic virotherapy is one potential solution to these barriers. Immune checkpoint inhibitors may facilitate immunogenic cell death by improving immune cell infiltration in cancer cells. PD-1 blockade shows better clinical outcomes for certain cancers. The addition of p53 to stimulate cell cycle arrest remains a novel field of research. The evaluated article by Araki et al. explores the efficacy of PD-1 blockade with oncolytic adenovirus platforms on immunogenic cell death and the possibility of combining PD-1 blockade and p53-activation. In vitro analysis showed increased cell death in multiple cell lines infected with AdV mediating p53 expression. The underlying process may attribute to apoptosis and autophagy, with evidence of increased immunogenic cell death. In vivo models demonstrated improved efficacy of p53-expressing AdV, particularly with the addition of PD-1 blockade which appears to be related to CD8+ cell infiltration.

A Comprehensive Review of the Current and Future Role of the Microbiome in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second most common cause of cancer death in the USA by 2030, yet progress continues to lag behind that of other cancers, with only 9% of patients surviving beyond 5 years. Long-term survivorship of PDAC and improving survival has, until recently, escaped our understanding. One recent frontier in the cancer field is the microbiome. The microbiome collectively refers to the extensive community of bacteria and fungi that colonise us. It is estimated that there is one to ten prokaryotic cells for each human somatic cell, yet, the significance of this community in health and disease has, until recently, been overlooked. This review examines the role of the microbiome in PDAC and how it may alter survival outcomes. We evaluate the possibility of employing microbiomic signatures as biomarkers of PDAC. Ultimately this review analyses whether the microbiome may be amenable to targeting and consequently altering the natural history of PDAC.

Effect of antireflux surgery for Barrett's esophagus: long-term results.

INTRODUCTION: Barrett's esophagus is a metaplastic change in the lower esophagus that results from long-standing gastro-esophageal reflux disease, associated with a risk of development of esophageal adenocarcinoma. This review examines the role of antireflux surgery in the management of Barrett's esophagus. EVIDENCE ACQUISITION: A systematic review of the EMBASE and MEDLINE databases (1974-2016) was undertaken to identify studies with long-term follow-up examining the role of antireflux surgery in Barrett's esophagus. Outcomes examined were: number of subjects, follow-up, rates of progression, regression and adenocarcinoma. Symptomatic outcomes, surgical morbidity and rates of surgical failure were included when available. EVIDENCE SYNTHESIS: A total of 2403 articles were identified of which 9 met the inclusion criteria for this study using the PRISMA methodology. Citation tracking identified 3 further studies for inclusion. There were 962 patients included in this study, 731 who were found to have completed endoscopic follow up with a total of 3736 years of follow up. Annual incidence of esophageal adenocarcinoma was found to be 0.18%. Thirty-five percent of patients (260 patients) had regression. Progression was seen in 8% (57 patients) postoperatively. There was no mortality. CONCLUSIONS: There is insufficient evidence to recommend surgery over medical therapy to reduce cancer risk in Barrett's esophagus. Regression of features associated with cancer risk was more common after surgery than medical therapy. Surgery has been shown to improve patients' gastroesophageal reflux disease-specific quality of life. Long-term, antireflux surgery represents a cost effective method to manage Barrett's Esophagus with continued endoscopic surveillance.