title: Barriers to drug delivery in interventional oncology.
abstract: Although much attention has been paid to mechanisms of anticancer drug resistance that focus on intracellular processes that protect tumor cells, it has recently become increasingly evident that the unique features of the tumor microenvironment profoundly impact the efficacy of cancer therapies. The properties of this extracellular milieu, including increased interstitial pressure, decreased pH, hypoxia, and abnormal vascularity, result in limited drug efficacy; this finding is true not only for systemic chemotherapy but also for catheter-based therapies, including chemoembolization and radioembolization. The present review summarizes the barriers to drug delivery imposed by the tumor microenvironment and provides methods to overcome these hurdles.
authors.affiliation: Department of Imaging, Division of Vascular Imaging and Intervention, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Rahul A
authors.initials: RA
authors.lastname: Sheth
authors.forename: Robin
authors.initials: R
authors.lastname: Hesketh
authors.forename: David S
authors.initials: DS
authors.lastname: Kong
authors.forename: Stephan
authors.initials: S
authors.lastname: Wicky
authors.forename: Rahmi
authors.initials: R
authors.lastname: Oklu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001692:Biological Transport; D002404:Catheterization; D015687:Cell Hypoxia; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008495:Medical Oncology / Q000379:methods*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010539:Permeability; D015641:Radiography, Interventional; D014018:Tissue Distribution; D016896:Treatment Outcome; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents
keywords: DEB; ECM; HIF; IFP; RF; VEGF; drug-eluting bead; extracellular matrix; hypoxia-inducible factor; interstitial fluid pressure; radiofrequency; vascular endothelial growth factor