Molecular characteristics and markers of advanced clear cell renal cell carcinoma: Pitfalls due to intratumoral heterogeneity and identification of genetic alterations associated with metastasis

2020 ◽  
Vol 27 (9) ◽  
pp. 790-797 ◽  
Author(s):  
Rebecca C Obeng ◽  
Rebecca S Arnold ◽  
Kenneth Ogan ◽  
Viraj A Master ◽  
John G Pattaras ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Genetic Alterations ◽  
Intratumoral Heterogeneity ◽  
Molecular Characteristics ◽  
Cell Renal Cell Carcinoma

scholarly journals The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What’s the Story Morning Glory?

2021 ◽  
Vol 22 (12) ◽  
pp. 6237
Author(s):  
Andrea Marchetti ◽  
Matteo Rosellini ◽  
Veronica Mollica ◽  
Alessandro Rizzo ◽  
Elisa Tassinari ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Treatment Algorithm ◽  
Morning Glory ◽  
Molecular Characteristics ◽  
Cell Renal Cell Carcinoma ◽  
Low Incidence

Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.

scholarly journals Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non–Clear Cell Renal Cell Carcinoma

2016 ◽  
Vol 34 (32) ◽  
pp. 3846-3853 ◽  
Author(s):  
Martin H. Voss ◽  
Ana M. Molina ◽  
Ying-Bei Chen ◽  
Kaitlin M. Woo ◽  
Joshua L. Chaim ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Genetic Alterations ◽  
Cell Renal Cell Carcinoma

Purpose The decreased effectiveness of single-agent targeted therapies in advanced non–clear cell renal cell carcinoma (ncRCC) compared with clear cell renal cell carcinoma (RCC) supports the study of combination regimens. We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC. Patients and Methods In this single-center phase II trial, treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks. The primary end point was progression-free survival (PFS) at 6 months. Correlative analyses explored candidate tissue biomarkers through next-generation sequencing. Results Thirty-five patients were enrolled with the following histologic subtypes: chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) RCC and unclassified RCC (uRCC, n = 23). The majority of patients had papillary growth as a major component (n = 14). For 34 evaluable patients, median PFS, overall survival, and objective response rate (ORR) were 11.0 months, 18.5 months, and 29%, respectively. PFS varied by histology ( P < .001), and ORR was higher in patients with significant papillary (seven of 18) or chromophobe (two of five) elements than for others (one of 11). Presence of papillary features were associated with benefit, including uRCC, where it correlated with ORR (43% v 11%), median PFS (12.9 v 1.9 months), and overall survival (28.2 v 9.3 months; P < .001). Several genetic alterations seemed to segregate by histology. In particular, somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants. All five patients achieved treatment benefit. Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features. Distinct mutational profiles among ncRCCs vary according to specific histology.

scholarly journals Characterization of the Prognostic Values of the CXCR1-7 in Clear Cell Renal Cell Carcinoma (ccRCC) Microenvironment

2020 ◽  
Vol 7 ◽  
Author(s):  
Zhulin Wu ◽  
Yingzhao Zhang ◽  
Xiang Chen ◽  
Wanjun Tan ◽  
Li He ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Chemokine Receptors ◽  
Clear Cell ◽  
Genetic Alterations ◽  
Functional Enrichment ◽  
Prognostic Biomarkers ◽  
Cell Renal Cell Carcinoma ◽  
Aberrant Expression

Background: As cancer immunotherapy has become a hot research topic, the values of CXC chemokine receptors (CXCRs) in tumor microenvironment have been increasingly realized. More and more evidence showed that the aberrant expression of CXCRs is closely related to the prognosis of various cancers. However, prognostic values and the exact roles of different CXCRs in clear cell renal cell carcinoma (ccRCC) have not yet been elucidated.Methods: To further evaluate the potential of seven CXCRs as prognostic biomarkers for ccRCC, multiple online analysis tools, including ONCOMINE, UALCAN (TCGA dataset), Kaplan–Meier Plotter, MethSurv, cBioPortal, GEPIA, Metascape, and TIMER databases, were utilized in our research.Results: The mRNA expression of CXCR4/6/7 was significantly increased in ccRCC patients, and all CXCRs are remarkably related to tumor stage or grade of ccRCC. Higher levels of CXCR3/4/5/6 expression were correlated with worse overall survival (OS) in patients with ccRCC, while higher expression of CXCR2 was associated with better OS. 23.14% mutation rate (118/510) of CXCR1-7 was observed in ccRCC patients, and the genetic alterations in CXCRs were related to worse OS and progression-free survival in ccRCC patients. Additionally, 53 CpGs of CXCR1-7 showed significant prognostic values. For functional enrichment, our results showed that CXCRs and their similar genes may be involved in cancer-associated pathways, immune process, and angiogenesis, etc. Besides, CXCRs were significantly correlated with multiple immune cells (e.g., CD8+ T cell, CD4+ cell, and dendritic cell).Conclusion: This study explored the potential prognostic values and roles of the CXCRs in ccRCC microenvironment. Our results suggested that CXCR4 and CXCR6 could be the prognostic biomarkers for the patients with ccRCC.

Smoking may cause genetic alterations at 5q22.2∼q23.1 in clear-cell renal cell carcinoma

2005 ◽  
Vol 163 (1) ◽  
pp. 7-11 ◽  
Author(s):  
Yoshihito Korenaga ◽  
Hideyasu Matsuyama ◽  
Hiroshi Hirata ◽  
Kazuhiro Nagao ◽  
Chietaka Ohmi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Genetic Alterations ◽  
Cell Renal Cell Carcinoma

scholarly journals Cancer Genetics and Therapeutic Opportunities in Urologic Practice

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 710
Author(s):  
Jacob J. Adashek ◽  
Alex Leonard ◽  
Jason Roszik ◽  
Arjun K. Menta ◽  
Giannicola Genovese ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cancer Genetics ◽  
Genetic Alterations ◽  
Genetic Associations ◽  
Cell Renal Cell Carcinoma ◽  
Molecular Alteration ◽  
Chromosome 3P

This article aims to summarize the current literature on genetic alterations related to tumors of the genitourinary tract. Novel associations have recently been reported between specific DNA alterations and genitourinary malignancies. The most common cause of chromosome 3p loss in clear cell renal cell carcinoma is a chromothripsis event, which concurrently generates a chromosome 5q gain. Specific patterns of clear cell renal cell carcinoma metastatic evolution have been uncovered. The first therapy targeting a specific molecular alteration has now been approved for urothelial carcinoma. Germline mutations in DNA damage repair genes and the transcription factor HOXB13 are associated with prostate cancer and may be targeted therapeutically. The genetic associations noted across different genitourinary cancers can inform potential screening approaches and guide novel targeted treatment strategies.

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