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 The Role of Everolimus in Renal Cell Carcinoma

2015 ◽  
Vol 2 (4) ◽  
pp. 187-194
Author(s):  
Malek Meskawi ◽  
Roger Valdivieso ◽  
Paolo Dell’Oglio ◽  
Vincent Trudeau ◽  
Alessandro Larcher ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Phase Iii ◽  
Current Evidence ◽  
Second Line ◽  
Cell Renal Cell Carcinoma ◽  
Line Therapy

Everolimus (RAD001) is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC). In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs). However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib), which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

Prognostic and predictive role of intra-tumoral CXCR1 expression in patients receiving tyrosine kinase inhibitors for metastatic clear-cell renal cell carcinoma

2021 ◽  
pp. 205141582110122
Author(s):  
Sridhar Panaiyadiyan ◽  
Brusabhanu Nayak ◽  
Prabhjot Singh ◽  
Seema Kaushal ◽  
Subhradip Karmakar ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

Objective: We aimed to evaluate the role of intra-tumoral CXCR1 expression in predicting prognosis and treatment response in metastatic clear-cell renal cell carcinoma patients receiving tyrosine kinase inhibitors. Materials and methods: Patients with metastatic clear-cell renal cell carcinoma presented between February 2018–December 2019 were studied for the CXCR1 expression in tumor tissues before starting tyrosine kinase inhibitors. Primary outcome measure was progression-free survival. Secondary outcome measures included overall survival and prediction of treatment response. Results: The study included 35 patients with a mean age of 53.6±9.6 years. At a mean follow-up of 12.2±4.1 months, 17 (48.6%) patients had disease progression including eight (22.9%) deaths. Patients with high CXCR1 expression, compared to those with low CXCR1 expression, had a significantly shorter 12-month progression-free survival (35.4% vs 77.9%, p=0.01) and an insignificant impact on 12-month overall survival. The CXCR1 expression scores significantly differed between patients with progressive and nonprogressive disease (20.1 vs 15.1, p=0.01) and patients with high CXCR1 expression had a reduced benefit from tyrosine kinase inhibitors. The multivariate Cox regression analysis showed CXCR1 expression as a significant predictor of progression-free survival. Conclusion: High intra-tumoral CXCR1 expression before tyrosine kinase inhibitors can be an independent prognostic factor for progression-free survival and predictor of reduced benefit in patients with metastatic clear-cell renal cell carcinoma. Level of evidence: Level 2b.

scholarly journals BRCA1-Associated Protein 1 (BAP-1) as a Prognostic and Predictive Biomarker in Clear Cell Renal Cell Carcinoma: A Systematic Review

Kidney Cancer ◽  
2021 ◽  
pp. 1-13
Author(s):  
Shuchi Gulati ◽  
Melissa Previtera ◽  
Maria F. Czyzyk-Krzeska ◽  
Primo Nery Lara
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Cell Renal Cell Carcinoma ◽  
Thymic Epithelial Tumors

BACKGROUND: The gene that encodes BRCA1-associated protein 1 (BAP1) has been reported to be dysregulated in several human cancers such as uveal melanoma, malignant pleural mesothelioma, hepatocellular carcinoma, thymic epithelial tumors, and clear-cell renal cell carcinoma (ccRCC). The gene is located on the human chromosome 3p21.3, encoding a deubiquitinase and acts as a classic two-hit tumor suppressor gene. BAP1 predominantly resides in the nucleus, where it interacts with several chromatin-associated factors, as well as regulates calcium signaling in the cytoplasm. As newer therapies continue to evolve for the management of RCC, it is important to understand the role of BAP1 mutation as a prognostic and predictive biomarker. OBJECTIVE: We aimed to systematically evaluate the role of BAP1 mutations in patients with RCC in terms of its impact on prognosis and its role as a predictive biomarker. METHODS: Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through March 2021. Titles and abstracts were screened to identify articles for full-text and then a descriptive review was performed. RESULTS: A total of 490 articles were initially identified. Ultimately 71 articles that met our inclusion criteria published between 2012–2021 were included in the analysis. Data were extracted and organized to reflect the role of BAP1 alterations as a marker of prognosis as well as a marker of response to treatments, such as mTOR inhibitors, VEGF tyrosine kinase inhibitors, and immune checkpoint inhibitors. CONCLUSIONS: Alterations in BAP1 appear to be uniformly associated with poor prognosis in patients with RCC. Knowledge gaps remain with regard to the predictive relevance of BAP1 alterations, especially in the context of immunotherapy. Prospective studies are required to more precisely ascertain the predictive value of BAP1 alterations in RCC.

scholarly journals Impact of COVID-19 pandemic on treatment patterns in metastatic clear cell renal cell carcinoma

ESMO Open ◽  
2020 ◽  
Vol 5 (Suppl 3) ◽  
pp. e000852 ◽  
Author(s):  
Stefanie Aeppli ◽  
Eric Innocents Eboulet ◽  
Tim Eisen ◽  
Bernard Escudier ◽  
Stefanie Fischer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Online Survey ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Treatment Decision ◽  
Risk Category ◽  
Cell Renal Cell Carcinoma ◽  
Risk Patients

BackgroundThe coronavirus pandemic has provoked discussions among healthcare providers how to manage cancer patients when faced with the threat of severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) infection. Immune checkpoint inhibitor (ICI) containing regimens are standard of care in the majority of metastatic clear cell renal cell carcinoma (mccRCC) patients. It remains unclear whether therapies should be modified in response to the COVID-19 pandemic.MethodsWe performed an online survey among physicians involved in the treatment of mccRCC, and 41 experts responded. Questions focused on criteria relevant for treatment decision outside the pandemic and the modifications of systemic therapy during COVID-19.FindingsFor the majority of experts (73%), the combination of International metastatic renal cell carcinoma Database Consortium (IMDC) risk category and patient fitness are two important factors for decision-making. The main treatment choice in fit, favourable risk patients outside the pandemic is pembrolizumab/axitinib for 53%, avelumab/axitinib, sunitinib or pazopanib for 13% of experts each. During the pandemic, ICI-containing regimens are chosen less often in favour of a tyrosine kinase inhibitors (TKI) monotherapy, mainly sunitinib or pazopanib (35%).In fit, intermediate/poor-risk patients outside the pandemic, over 80% of experts choose ipilimumab/nivolumab, in contrast to only 41% of physicians during COVID-19, instead more TKI monotherapies are given. In patients responding to established therapies with ICI/ICI or ICI/TKI combinations, most participants modify treatment regimen by extending cycle length, holding one ICI or even both.ConclusionmccRCC treatment modifications in light of the coronavirus pandemic are variable, with a shift from ICI/ICI to ICI/TKI or TKI monotherapy.

Survival of patients with papillary type II renal cell carcinoma treated with tyrosine-kinase inhibitors: A comparison with clear cell histologies.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 511-511 ◽  
Author(s):  
Jozefina Casuscelli ◽  
Alexander Buchner ◽  
Bernadett Szabados ◽  
Christian G. Stief ◽  
Michael D. Staehler
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Primary Tumor ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Type Ii ◽  
Cell Renal Cell Carcinoma ◽  
Papillary Type

511 Background: The sequential use of Tyrosine-kinase inhibitors leads to a longer survival in patients with clear-cell renal cell carcinoma (ccRCC). However to-date there is little data available on the survival of patients with non-clear-cell RCC treated with TKI. We focused on papillary type II renal cell carcinoma (papIIRCC) and assessed the outcome of our patients with metastatic disease on systemic treatment. The outcome was compared with our patients with clear cell histology. Methods: Patients with histologic evidence of papillary type II renal cell carcinoma or clear cell renal cell carcinoma were treated with single agent sunitinib or sorafenib. Progression free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier curves. Patients were identified from an institutional database and had to have a follow up of ≥2 years. Subgroup analyses were performed to determine the influence of primary tumor stage and cell differentiation on PFS and OS. Results: 18 patients with papIIRCC received sunitinib (16) or sorafenib (2) while 166 patients with ccRCC were treated with sunitinib (78%) or sorafenib (22%). Median PFS for papIIRCC is 8.9 mos, for ccRCC it is 11 mos. OS for papIIRCC is 15 mos, while ccRCC show an OS of 32 mos. The same tendency for longer PFS and OS is seen in ccRCC patients with low primary tumor grade and highly differentiated carcinomas, whereas large tumors and low differentiation determine a poor prognosis in both groups. Conclusions: Most papIIRCC patients have a poor outcome and shorter PFS than ccRCC on the same therapy. They benefit from the TKI therapy, but the survival is clearly reduced compared with ccRCC patients. This may be due to the poor prognosis of the papillary type II histology, but the assumption is that the administered therapy is not conceived for this type of RCC. Future studies are required to determine the optimal therapy for papillary type II renal cell cancer.

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