New avenues in pancreatic cancer: exploiting microRNAs as predictive biomarkers and new approaches to target aberrant metabolism

ABSTRACT

Introduction: Most pancreatic cancer patients are diagnosed at advanced-stages and first-line regimens (FOLFIRINOX and gemcitabine/nab-paclitaxel) provide limited survival advantage and are associated with considerable toxicities. In this grim scenario, novel treatments and biomarkers are warranted.

Areas covered: MicroRNAs (miRNAs) emerged as biomarkers for cancer prognosis and chemoresistance and blood-based miRNAs are being evaluated as indicators of therapeutic activity. Moreover, aberrant metabolism, such as aerobic glycolysis, has been correlated to tumor aggressiveness and poor prognosis. Against this background, innovative approaches to tackle metabolic aberrations are being implemented and glycolytic inhibitors targeting lactate dehydrogenase-A (LDH-A) showed promising effects in preclinical models. A PubMed search was used to compile relevant publications until February 2019.

Expert opinion: Analysis of tissue/circulating miRNA might improve selection for optimal treatment regimens. For instance, miR-181a modulation seems to predict response to FOLFIRINOX. However, we need further studies to validate predictive miRNA profiles, as well as to exploit miRNAs for treatment-tailoring. Several miRNAs have also a key role in regulating metabolic aberrations. Since preliminary evidence supports the development of new agents targeting these aberrations, such as LDH-A inhibitors, the identification of biomarkers for these treatments, including the above-mentioned miRNAs, should shorten the gap between preclinical studies and personalized therapies.

KEYWORDS:

• FOLFIRINOX
• gemcitabine
• metabolic reprogramming
• microRNAs
• nab-paclitaxel pancreatic cancer
• Warburg effect

Article Highlights

• Pancreatic cancer has a dismal prognosis mostly due to late diagnosis and poor efficacy of current treatments: new treatments and biomarkers are warranted

• MicroRNAs (miRNAs) are emerging as predictive biomarkers of response and should be investigated to optimize new therapeutic strategies

• Innovative approaches to tackle cancer metabolic aberrations, such as glycolytic inhibitors targeting lactate dehydrogenase-A (LDH-A), showed promising effects in preclinical models

• The parallel development of new drugs targeting LDH-A and of biomarkers for these treatments, including miRNAs, should shorten the gap between preclinical studies and personalized therapies.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

Funding from Italian Association for Italian Research (AIRC Start-Up grant) and Fondazione Pisana per la Scienza grant.