title: Nanotechnologies for the treatment of colon cancer: From old drugs to new hope.
abstract: Colorectal cancer is a wide-reaching health problem due to its incidence and to the high mortality rates. Adjuvant chemotherapies have considerably improved the prognosis and/or the overall survival of patients with locally advanced and metastatic cancers. Nevertheless, their efficiency remains limited due to intrinsic and emerging multidrug resistance (MDR) of cancer cells, and to major adverse effects and dose limiting toxicities. The present review discusses the knowledge of clinically relevant mechanisms of resistance to cytotoxic and targeted therapies for the treatment of colorectal cancer, and focuses on the benefit of nanomedicine approach to circumvent these processes. Nanomedicaments should allow extensive cancer cell drug loading independent on cell surface transporters, -thus overwhelming drug metabolism and efflux-, but also alleviate side-effects related to tissue-dependent drug uptake. Finally, we provide an outline of preclinical and clinical studies of nanoparticles formulations for colorectal cancer treatment, and briefly discuss strategies to optimize the selective delivery of these nanomedicines to colorectal cancer cells.
authors.affiliation: Université Paris-Sud XI, Faculté de Pharmacie, UMR CNRS 8612, 92296 Châtenay-Malabry, France; INSERM, U1149, CNRS ERL8252, Centre de Recherche sur l'Inflammation, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Site Bichat, Paris, France.
authors.forename: Larissa
authors.initials: L
authors.lastname: Kotelevets
authors.affiliation: INSERM, U1149, CNRS ERL8252, Centre de Recherche sur l'Inflammation, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence Inflamex, DHU FIRE, Faculté de Médecine, Site Bichat, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chastre
authors.affiliation: Université Paris-Sud XI, Faculté de Pharmacie, UMR CNRS 8612, 92296 Châtenay-Malabry, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaële
authors.affiliation: Université Paris-Sud XI, Faculté de Pharmacie, UMR CNRS 8612, 92296 Châtenay-Malabry, France. Electronic address: patrick.couvreur@u-psud.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D050997:Nanomedicine / Q000379:methods*; D036103:Nanotechnology / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents
keywords: Chemotherapy; Clinical trials; Colorectal cancer; Multidrug resistance; Nanomedicine; Nanoparticles; Transporters