First-line treatment of metastatic renal cell carcinoma: current standard of care

SummaryThe introduction of immune checkpoint inhibitors has further improved response and survival rates in patients with metastatic renal cell carcinoma. In this context, the most promising trial results in the past 12 months include KEYNOTE 426 and the 30-month update of CheckMate 214. Both trials, similar to IMmotion 151 and JAVELIN Renal 101, reported improved survival and response data. CheckMate 214 reported an overall survival benefit in intermediate and poor risk patients, however, such benefit was observed irrespective of conventional risk groups in KEYNOTE 426. These results prompted the European Association of Urology (EAU) to update their guidelines on the treatment of metastatic renal cell carcinoma and to recommend the combinations pembrolizumab/axitinib and nivolumab/ipilimumab as standard of care in previously untreated intermediate and poor risk patients and the combination pembrolizumab/axitinib as standard of care in previously untreated favorable risk patients. Inflammatory and angiogenic markers profiles may have the potential to become a tool aiding to better individualize treatment regimens in the future. Exploratory analyses of the IMmotion 151 trial present first results supporting such approach. Sarcomatoid variant histology remains an unfavorable prognostic parameter. Subgroup analyses of CheckMate 214 revealed exceptional response in patients with sarcomatoid histology. Whereas conventional therapy was inferior in such patients, more than 50% of pa...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research

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Conclusions: The results of the present retrospective study demonstrate the suitability of the MSKCC model in mRCC patients treated with first-line sunitinib and suggest different outcomes between patients with one or two risk factors.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Hypoxia-inducible transcription factors (HIFs) directly dictate the expression of multiple RNA species including novel and as yet uncharacterized long noncoding transcripts with unknown function. We used pan-genomic HIF-binding and transcriptomic data to identify a novel long noncoding RNA Noncoding Intergenic Co-Induced transcript (NICI) on chromosome 12p13.31 which is regulated by hypoxia via HIF-1 promoter-binding in multiple cell types. CRISPR/Cas9-mediated deletion of the hypoxia-response element revealed co-regulation of NICI and the neighboring protein-coding gene, solute carrier family 2 member 3 (SLC2A3) which enc...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Gene Regulation Source Type: research
AKI promotes the development of papillary renal cell carcinoma from single progenitors
Source: The Doctors Lounge - Oncology - Category: Cancer & Oncology Tags: Nephrology, Oncology, Pathology, Journal, Source Type: news
Conclusion: Our study reveals that miR-206 functions as a tumor metastasis suppressor and sheds new light on the clinical significance of miR-206 in NSCLC therapy. PMID: 32206066 [PubMed - in process]
Source: Cellular and Molecular Biology Letters - Category: Biochemistry Authors: Tags: Cell Mol Biol Lett Source Type: research
AbstractThe purpose of this study is to evaluate the expression and the prognostic role of main factors, involved in the hypoxia pathway, in patients with clear-cell renal cell carcinoma (ccRCC). Immunohistochemical expression of Hypoxia inducible factors (HIF) HIF-1a, HIF-2a, prolyl hydroxylases PHD1, PHD2, PHD3, and factor inhibiting HIF (FIH) was assessed on a tissue microarray, containing tumour and corresponding normal kidney tissue from 66 patients underwent surgery for ccRCC. Expression levels were evaluated in relation to T stage, Fuhrman grade, cancer-specific, and overall survival (OS). Cytoplasmatic expression o...
Source: Medical Molecular Morphology - Category: Molecular Biology Source Type: research
Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
Authors: Dai L, Chen L, Wang W, Lin P Abstract Context: The relationship between resveratrol and histone acetylation in renal cell carcinoma (RCC) has not yet been reported.Objective: To explore the functional role of resveratrol in RCC.Materials and methods: Functional experiments were performed to determine proliferatio n of ACHN cells with treatment of resveratrol (0, 7.8125, 15.625, 31.25 and 62.5 μg/mL, for 12, 24 and 48 h of culture) or 0.1 μM SAHA. The enzyme activities of MMP-2/-9 were measured by gelatine zymography and histone acetylation by Western blot.Results: When the cells ...
Source: Pharmaceutical Biology - Category: Drugs & Pharmacology Tags: Pharm Biol Source Type: research
Source: Cancer Management and Research - Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research
To investigate the expression and function of RSK4, MMP-9 and CD44 in primary clear cell renal cell carcinoma (primary ccRCC) and metastatic clear cell renal cell carcinoma (metastatic ccRCC), as well as the c...
Source: Diagnostic Pathology - Category: Pathology Authors: Tags: Research Source Type: research
Source: International Urology and Nephrology - Category: Urology & Nephrology Source Type: research
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