title: The relevance of testing the efficacy of anti-angiogenesis treatments on cells derived from primary tumors: a new method for the personalized treatment of renal cell carcinoma.
abstract: Despite the numerous available drugs, the most appropriate treatments for patients affected by common or rare renal cell carcinomas (RCC), like those associated with the Xp11.2 translocation/transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3) gene fusion (TFE3 RCC), are not clearly defined. We aimed to make a parallel between the sensitivity to targeted therapies on living patients and on cells derived from the initial tumor. Three patients diagnosed with a metastatic RCC (one clear cell RCC [ccRCC], two TFE3 RCC) were treated with anti-angiogenesis drugs. The concentrations of the different drugs giving 50% inhibition of cell proliferation (IC50) were determined with the Thiazolyl Blue Tetrazolium Bromide (MTT) assay on cells from the primary tumors and a reference sensitive RCC cell line (786-O). We considered the cells to be sensitive if the IC50 was lower or equal to that in 786-O cells, and insensitive if the IC50 was higher to that in 786-O cells (IC 50 of 6 ± 1 µM for sunitinib, 10 ± 1 µM for everolimus and 6 ± 1 µM for sorafenib). Based on this standard, the response in patients and in cells was equivalent. The efficacy of anti-angiogenesis therapies was also tested in cells obtained from five patients with non-metastatic ccRCC, and untreated as recommended by clinical practice in order to determine the best treatment in case of progression toward a metastatic grade. In vitro experiments may represent a method for evaluating the best first-line treatment for personalized management of ccRCC during the period following surgery.
authors.affiliation: Biomedical Research Unit, Centre Scientifique of Monaco, Principality of Monaco.
authors.forename: Renaud
authors.initials: R
authors.lastname: Grépin
authors.affiliation: Institute for Research on Cancer and Aging of Nice (IRCAN) UMR/7284 U1081, Nice University Hospital, Central Laboratory of Pathology, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Ambrosetti
authors.affiliation: Institute for Research on Cancer and Aging of Nice (IRCAN) UMR/7284 U1081, Nice University Hospital, Department of Urology, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Marsaud
authors.affiliation: Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France.
authors.forename: Lauris
authors.initials: L
authors.lastname: Gastaud
authors.affiliation: Nice University Hospital, Department of Urology, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Amiel
authors.affiliation: Institute for Research on Cancer and Aging of Nice (IRCAN) UMR/7284 U1081, Nice University Hospital, Laboratory of Solid Tumors Genetics, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
authors.affiliation: Institute for Research on Cancer and Aging of Nice (IRCAN) UMR/7284 U1081, University of Nice Sophia Antipolis, Nice, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Pagès
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D057285:Precision Medicine; D011758:Pyrroles / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000077157:Sorafenib; D000077210:Sunitinib; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; C069203:TFE3 protein, human; D009536:Niacinamide; D000077157:Sorafenib; D020794:Receptor Protein-Tyrosine Kinases; D000077210:Sunitinib