Therapeutic Approaches for Metastatic Pancreatic Adenocarcinoma

Rubinson, Douglas A.; Wolpin, Brian M.

doi:10.1016/j.hoc.2015.04.012

Cited by 12 publications

(7 citation statements)

References 57 publications

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“…35 However, a low dose of simvastatin was administered, and multi-agent chemotherapy programs have become the standard of care for advanced pancreatic cancer, rather than single-agent gemcitabine. 36…”

Section: Discussionmentioning

confidence: 99%

Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer

Hamada

Khalaf

Yuan

et al. 2018

Clinical Gastroenterology and Hepatology

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Section: Discussionmentioning

confidence: 99%

Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer

Hamada

Khalaf

Yuan

et al. 2018

Clinical Gastroenterology and Hepatology

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“…Thus, disruption of crucial driver genes creates a complex tumorigenic network that is expected to greatly alter the systems biology of the cell. An improved understanding of this altered system could be exploited to identify unique vulnerabilities and target specific mutant proteins or pathways 76 .…”

Section: Clonal Expansionmentioning

confidence: 99%

Pancreatic cancer biology and genetics from an evolutionary perspective

2016

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Cancer is an evolutionary disease, containing the hallmarks of an asexually reproducing unicellular organism subject to evolutionary paradigms. Pancreatic ductal adenocarcinoma (hereafter referred to as pancreatic cancer) is a particularly robust example of this phenomenon. Genomic features indicate that pancreatic cancer cells are selected for fitness advantages when encountering the geographic and resource-depleted constraints of the microenvironment. Phenotypic adaptations to these pressures help disseminated cells to survive in secondary sites, a major clinical problem for patients with this disease. In this Review we gather the wide-ranging aspects of pancreatic cancer research into a single concept rooted in Darwinian evolution, with the goal of identifying novel insights and opportunities for study.

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“…In the last two decades, gemcitabine has been the mainstay of first-line therapy for unresectable locally advanced or metastatic pancreatic cancer [ 2 ]. Recently, FOLFIRINOX (Folinic Acid, 5-FU, Irinotecan, and Oxaliplatin) or gemcitabine in combination with nab-paclitaxel have shown greater efficacy than gemcitabine alone and are now standard treatment options for metastatic disease [ 3 , 4 , 5 ]. FOLFIRONOX improved median overall survival (OS) to 11.1 months with 1-year survival rate of 48.4% when compared to gemcitabine alone with 6.8 months and 20.6%, respectively [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

A Phase II Study of Pelareorep (REOLYSIN®) in Combination with Gemcitabine for Patients with Advanced Pancreatic Adenocarcinoma

Mahalingam

Goel

Aparo

et al. 2018

Cancers

101

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Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with 1 and 5-year survival rates of ~18% and 7% respectively. FOLFIRINOX or gemcitabine in combination with nab-paclitaxel are standard treatment options for metastatic disease. However, both regimens are more toxic than gemcitabine alone. Pelareorep (REOLYSIN®), a proprietary isolate of reovirus Type 3 Dearing, has shown antitumor activity in clinical and preclinical models. In addition to direct cytotoxic effects, pelareorep can trigger antitumor immune responses. Due to the high frequency of RAS mutations in PDAC, we hypothesized that pelareorep would promote selective reovirus replication in pancreatic tumors and enhance the anticancer activity of gemcitabine. Chemotherapy-naïve patients with advanced PDAC were eligible for the study. The primary objective was Clinical Benefit Rate (complete response (CR) + partial response (PR) + stable disease (SD) ≥ 12 weeks) and secondary objectives include overall survival (OS), toxicity, and pharmacodynamics (PD) analysis. The study enrolled 34 patients; results included one partial response, 23 stable disease, and 5 progressive disease. The median OS was 10.2 months, with a 1- and 2-year survival rate of 45% and 24%, respectively. The treatment was well tolerated with manageable nonhematological toxicities. PD analysis revealed reovirus replication within pancreatic tumor and associated apoptosis. Upregulation of immune checkpoint marker PD-L1 suggests future consideration of combining oncolytic virus therapy with anti-PD-L1 inhibitors. We conclude that pelareorep complements single agent gemcitabine in PDAC.

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Therapeutic Approaches for Metastatic Pancreatic Adenocarcinoma

Cited by 12 publications

References 57 publications

Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer

Prediagnosis Use of Statins Associates With Increased Survival Times of Patients With Pancreatic Cancer

Pancreatic cancer biology and genetics from an evolutionary perspective

A Phase II Study of Pelareorep (REOLYSIN®) in Combination with Gemcitabine for Patients with Advanced Pancreatic Adenocarcinoma

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