TY - JOUR
T1 - New avenues in pancreatic cancer: exploiting microRNAs as predictive biomarkers and new approaches to target aberrant metabolism
AU - Capula, Mjriam
AU - Mantini, Giulia
AU - Funel, Niccola
AU - Giovannetti, Elisa
PY - 2019/12/2
Y1 - 2019/12/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85075381485&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31721608
U2 - https://doi.org/10.1080/17512433.2019.1693256
DO - https://doi.org/10.1080/17512433.2019.1693256
M3 - Article
C2 - 31721608
SN - 1751-2433
VL - 12
SP - 1081
EP - 1090
JO - Expert Review of Clinical Pharmacology
JF - Expert Review of Clinical Pharmacology
IS - 12
ER -