scholarly journals Metabolomic Profiling in Renal Cell Carcinoma Patients: News and Views

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5229
Author(s):  
Gaetano Aurilio ◽  
Matteo Santoni ◽  
Francesco Massari ◽  
Alessia Cimadamore ◽  
Alessandro Rizzo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Large Scale ◽  
Clear Cell ◽  
Clinical Investigation ◽  
Treatment Strategies ◽  
Akt Signaling ◽  
Tyrosine Kinase Domain ◽  
Metabolomic Profiling

Background: We address novelty regarding metabolomic profiling in renal cell carcinoma (RCC) patients, in an attempt to postulate potential treatment strategies. Methods: A large-scale literature search in existing scientific websites focusing on the keywords “renal cell carcinoma”, “clear cell histology”, “papillary histology”, “metabolomic profiling”, and “therapeutics” was performed. Results: The PI3K/Akt signaling pathway is key in clear cell RCC metabolism and accordingly several drugs are presently available for routine use in clinical practice. Along this line, new treatment combinations against PI3K/Akt family members are currently under clinical investigation. On the other hand, new developed targets such as c-Met tyrosine kinase domain, glutathione (GSH) metabolism, and histone deacetylases enzymes (HDAC), as well as therapeutic strategies targeting them are currently being tested in clinical trials and here discussed. Conclusions: In RCC patients, the PI3K/Akt signaling is still the most effective targetable pathway. Targeting other metabolic pathways such as c-Met, GSH, and HDAC appears to be a promising approach and deserve further insights.

Exploiting Synthetic Lethal Network for Precision Treatment of Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Zhicheng Liu ◽  
Dongxu Lin ◽  
Linmeng Zhang ◽  
Chen Yang ◽  
Bin Guo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Large Scale ◽  
Target Genes ◽  
Clear Cell ◽  
Therapeutic Potential ◽  
Synthetic Lethality ◽  
Treatment Modalities ◽  
Cell Renal Cell Carcinoma

Abstract Background The emerging of targeted therapies has revolutionized the treatment modalities of advanced clear cell renal cell carcinoma (ccRCC) over the past fifteen years. However, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles of ccRCC cohorts were exploited for conducting an integrative analysis. Method Based on synthetic lethality (SL), a concept that simultaneous losses of two genes cause cell death while a single loss does not, we sought to develop a computational pipeline to infer potential SL partners of ccRCC. Drug response prediction were received from three pharmacological databases to select agents which are likely to be effective in precisely treating patients with target gene mutation. Results We developed a credible method to identify SL pairs and determined a list of 72 candidate pairs which might be utilized to selectively eliminate tumors with genetic aberrations through SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medicine targets for patients with BAP1 mutations. After mapping these target genes to comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potential in BAP1 mutant tumors. Conclusion Overall, our findings provide insight into the overview of ccRCC mutation patterns and offer novel opportunities for improving individualized cancer treatment.

PTPN13 acts as a tumor suppressor in clear cell renal cell carcinoma by inactivating Akt signaling

2020 ◽  
Vol 396 (1) ◽  
pp. 112286
Author(s):  
Qingzhi Long ◽  
Jiping Sun ◽  
Jia Lv ◽  
Yu Liang ◽  
Huixian Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Akt Signaling ◽  
Cell Renal Cell Carcinoma

scholarly journals Consensus paper: current state of first- and second-line therapy in advanced clear-cell renal cell carcinoma

2020 ◽  
Vol 16 (29) ◽  
pp. 2307-2328
Author(s):  
Peter J Goebell ◽  
Philipp Ivanyi ◽  
Jens Bedke ◽  
Lothar Bergmann ◽  
Dominik Berthold ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Second Line ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
New Treatments

The therapy of advanced (clear-cell) renal cell carcinoma (RCC) has recently experienced tremendous changes. Several new treatments have been developed, with PD-1 immune-checkpoint inhibition being the backbone of therapy. Diverse immunotherapy combinations change current first-line standards. These changes also require new approaches in subsequent lines of therapy. In an expert panel, we discussed the new treatment options and how they change clinical practice. While first-line immunotherapies introduce a new level of response rates, data on second-line therapies remains poor. This scenario poses a challenge for clinicians as guideline recommendations are based on historical patient cohorts and agents may lack the appropriate label for their in guidelines recommended use. Here, we summarize relevant clinical data and consider appropriate treatment strategies.

scholarly journals The epigenetic landscape of clear-cell renal cell carcinoma

2015 ◽  
Vol 2 (3) ◽  
pp. 90-104 ◽  
Author(s):  
Katarzyna Kluzek ◽  
Hans Antonius Bluyssen ◽  
Joanna Wesoly
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Large Scale ◽  
Clear Cell ◽  
Kidney Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Chromosome 3P ◽  
Recurrent Mutations ◽  
Novel Therapeutic Strategies

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of all kidney tumors. During the last few years, epigenetics has emerged as an important mechanism in ccRCC pathogenesis. Recent reports, involving large-scale methylation and sequencing analyses, have identified genes frequently inactivated by promoter methylation and recurrent mutations in genes encoding chromatin regulatory proteins. Interestingly, three of detected genes (PBRM1, SETD2 and BAP1) are located on chromosome 3p, near the VHL gene, inactivated in over 80% ccRCC cases. This suggests that 3p alterations are an essential part of ccRCC pathogenesis. Moreover, most of the proteins encoded by these genes cooperate in histone H3 modifications. The aim of this review is to summarize the latest discoveries shedding light on deregulation of chromatin machinery in ccRCC. Newly described ccRCC-specific epigenetic alterations could potentially serve as novel diagnostic and prognostic biomarkers and become an object of novel therapeutic strategies.

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