The microbiome of pancreatic cancer: from molecular diagnostics to new therapeutic approaches to overcome chemoresistance caused by metabolic inactivation of gemcitabine

ABSTRACT

Introduction: Pancreatic cancer is a complex disease, with an extremely poor response to chemotherapy. Emerging evidence indicates that the tumor microenvironment (TME) might play an important role in mediating chemoresistance.

Areas covered: The evaluated study by Geller and collaborators describes several bacterial species within pancreatic tumor tissues and TME and investigated their roles in gemcitabine chemoresistance. Intratumor bacteria express the enzyme cytidine deaminase (CDD), whose long form (CDD_L) was shown to metabolize gemcitabine into its inactive metabolite. CDD_L is mostly expressed by Gammaproteobacteria and this was among the most common species in pancreatic cancer tissues. Interestingly, mouse models of colorectal cancer injected with bacterial CDD_L displayed a reduced response to gemcitabine, but this resistance was neutralized by the antibiotic ciprofloxacin.

Expert Commentary: The increased knowledge on the microbiome in pancreatic tissues, as well as its role in chemoresistance, will provide innovative prognostic and therapeutic strategies.

KEYWORDS:

• Aggregatibacter actinomycetemcomitans
• chronic periodontitis
• cytidine deaminase
• Notch-1
• Notch-1
• Porphyromonas gingivalis

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was partly supported by Cancer Center Amsterdam Foundation grant 2016 [GK, EG], Bennink Foundation (EG, LM, GK) and Italian Association for Cancer Research, Associazione Italiana per la Ricerca sul Cancro Start-Up Grant [EG]. SC is beneficiary of an AXA Research Fund Post-doctoral grant.