ABC transporters as molecular effectors of pancreatic oncogenic pathways: the Hedgehog-GLI model

Chemoresistance is the main cause of disease progression and mortality among patients diagnosed from pancreatic adenocarcinoma. Nowadays, most patients are diagnosed with advanced disease, and chemotherapy becomes the corner stone of care, looking for clinical benefit and improvement in survival. However, response rates are low, and disease outcome is very short, needing for new drugs that overcome resistance.

Till date, one of the better known mechanisms of drug resistance in cancer is related to ATP-binding cassette (ABC) transporters, highly expressed in solid tumors and, moreover, in cancer stem cells. These cancer stem cells are thought to be responsible for tumor maintenance, progression, and relapse of the disease due, in part, to an exhibition of multiple resistance mechanisms to chemotherapy and radiation.

In order to remove this cancer stem cell population within the tumors, it is imperative to look for new molecular pathways involved in pancreatic carcinogenesis and stemness. In this study, we suggest a potential role of hedgehog-GLI pathway in pancreatic cancer chemoresistance, based on ABC transporters' overexpression.