title: Future perspectives for mTOR inhibitors in renal cell cancer treatment.
abstract: Everolimus is a mTOR inhibitor that demonstrates antitumor and antiangiogenic activities. In a randomized Phase III trial, patients with metastatic renal cell carcinoma who progressed on sunitinib/sorafenib were treated with everolimus and showed significant improvement in progression-free survival compared with best supportive care. Novel approaches in treatment are expected to ensure less toxic therapies and increase efficacy of everolimus. To provide a new perspective for mTOR inhibitor research and therapy, we discuss renal cell carcinoma cancer stem cells as a potential target for mTOR inhibitors and present new concepts on emerging antiangiogenic therapies. Finally, we point why systems biology approach with reverse molecular engineering may also contribute to the field of drug discovery in renal cell carcinoma.
authors.affiliation: Department of Oncology with Laboratory of Molecular Oncology, Military Institute of Medicine, Szaserow 128, 04-141, Warsaw, Poland.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Czarnecka
authors.forename: Anna
authors.initials: A
authors.lastname: Kornakiewicz
authors.forename: Fei
authors.initials: F
authors.lastname: Lian
authors.forename: Cezary
authors.initials: C
authors.lastname: Szczylik
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases
keywords: RAD001; RECORD; afinitor; combination treatment; everolimus; mTOR; renal cell cancer