title: Heat-Shock Protein 90-Targeted Nano Anticancer Therapy.
abstract: Suboptimal chemotherapy of anticancer drugs may be attributed to a variety of cellular mechanisms, which synergize to dodge the drug responses. Nearly 2 decades of heat-shock protein 90 (Hsp90)-targeted drug discovery has shown that the mono-therapy with Hsp90 inhibitors seems to be relatively ineffective compared with combination treatment due to several cellular dodging mechanisms. In this article, we have tried to analyze and review the Hsp90 and mammalian target of rapamycin (m-TOR)-mediated drug resistance mechanisms. By using this information we have discussed about the rationale behind use of drug combinations that includes both or any one of these inhibitors for cancer therapy. Currently, biodegradable nano vector (NV)-loaded novel drug delivery systems have shown to resolve the problems of poor bioavailability. NVs of drugs such as paclitaxel, doxorubicin, daunorubicin, and others have been successfully introduced for medicinal use. Hence, looking at the success of NVs, in this article we have also discussed the progress made in the delivery of biodegradable NV-loaded Hsp90 and m-TOR-targeted inhibitors in multiple drug combinations. We have also discussed the possible ways by which the market success of biodegradable NVs can positively impact the clinical trials of anti-Hsp90 and m-TOR combination strategy.
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary Science, Toyo University, Kawagoe, Saitama-350-8585, Japan.
authors.forename: Ankit K
authors.initials: AK
authors.lastname: Rochani
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary Science, Toyo University, Kawagoe, Saitama-350-8585, Japan.
authors.forename: Aswathy
authors.initials: A
authors.lastname: Ravindran Girija
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary Science, Toyo University, Kawagoe, Saitama-350-8585, Japan.
authors.forename: Ankita
authors.initials: A
authors.lastname: Borah
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary Science, Toyo University, Kawagoe, Saitama-350-8585, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Maekawa
authors.affiliation: Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary Science, Toyo University, Kawagoe, Saitama-350-8585, Japan. Electronic address: sakthi@toyo.jp.
authors.forename: D
authors.initials: D
authors.lastname: Sakthi Kumar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: biomaterials; cancer; cancer chemotherapy; drug resistance; nanoparticles; nanotechnology