Everolimus for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC)

Expert Opin Investig Drugs. 2019 Jul;28(7):583-592. doi: 10.1080/13543784.2019.1632289. Epub 2019 Jun 21.

Abstract

Introduction: PDAC is a lethal malignancy with a clear unmet need; almost all patients fail 1st, 2nd, and 3rd line multi-agent cytotoxic chemotherapy. The mammalian target of rapamycin (mTOR) has been identified as a key signaling node enhancing tumor survival and drug resistance in PDAC; hence, it is considered a promising therapeutic target. Areas covered: We comprehensively reviewed the evidence from preclinical and phase I and II clinical trials, based on the authors'clinical experience and a PubMed, Cochrane library, Embase, and Google Scholar search everolimus + pancreatic cancer. Expert opinion: Everolimus has not demonstrated efficacy in PDAC; however, an mTOR inhibitor in combination with stroma-targeted therapies may be a promising area to explore in clinical trials.

Keywords: Everolimus; mTOR; pancreatic adenocarcinoma.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / pathology
  • Drug Resistance, Neoplasm
  • Everolimus / administration & dosage*
  • Everolimus / pharmacology
  • Humans
  • Molecular Targeted Therapy
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Survival
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Everolimus
  • MTOR protein, human
  • TOR Serine-Threonine Kinases