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Giornale Italiano Di Nefrologia :... Jun 2022Renal cell carcinoma (RCC) is the most common type of urogenital cancer. It has a mortality rate of 30-40% and is more commonly seen in men than women. In addition to... (Review)
Review
Renal cell carcinoma (RCC) is the most common type of urogenital cancer. It has a mortality rate of 30-40% and is more commonly seen in men than women. In addition to gender, other risk factors of RCC include obesity, hypertension, smoking, and chronic kidney disease. Following the improvements in diagnostic tests, such as CT and MRI imaging, the incidence of patients diagnosed with RCC has rapidly increased over the past decades. The most common type of RCC, based on histological and molecular subtypes, is clear cell carcinoma which occurs frequently due to mutations in the VHL gene. Nephron-sparing surgery is a selective technique to maintain kidneys in patients while radical nephrectomy and partial nephrectomy are used to remove small tumors. In addition to surgical approaches, adjuvant therapy and targeted therapy are applied in patients with metastatic RCC. In this review, we give an overview of the most recent research on RCC which would help physicians to better manage patients with RCC.
Topics: Carcinoma, Renal Cell; Combined Modality Therapy; Female; Humans; Kidney; Kidney Neoplasms; Male; Nephrectomy
PubMed: 35819037
DOI: No ID Found -
Nature Reviews. Nephrology Apr 2021The molecular features that define clear cell renal cell carcinoma (ccRCC) initiation and progression are being increasingly defined. The TRACERx Renal studies and... (Review)
Review
The molecular features that define clear cell renal cell carcinoma (ccRCC) initiation and progression are being increasingly defined. The TRACERx Renal studies and others that have described the interaction between tumour genomics and remodelling of the tumour microenvironment provide important new insights into the molecular drivers underlying ccRCC ontogeny and progression. Our understanding of common genomic and chromosomal copy number abnormalities in ccRCC, including chromosome 3p loss, provides a mechanistic framework with which to organize these abnormalities into those that drive tumour initiation events, those that drive tumour progression and those that confer lethality. Truncal mutations in ccRCC, including those in VHL, SET2, PBRM1 and BAP1, may engender genomic instability and promote defects in DNA repair pathways. The molecular features that arise from these defects enable categorization of ccRCC into clinically and therapeutically relevant subtypes. Consideration of the interaction of these subtypes with the tumour microenvironment reveals that specific mutations seem to modulate immune cell populations in ccRCC tumours. These findings present opportunities for disease prevention, early detection, prognostication and treatment.
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Mutation; Prognosis; Tumor Microenvironment
PubMed: 33144689
DOI: 10.1038/s41581-020-00359-2 -
Pathologica Feb 2022The World Health Organization (WHO) 2022 classification of urinary and male genital tumours (5th edition) has significantly improved our understanding of the... (Review)
Review
The World Health Organization (WHO) 2022 classification of urinary and male genital tumours (5th edition) has significantly improved our understanding of the morphologic, immunohistochemical, and molecular characteristics of renal tumours. The aim of this review is to outline the most important changes and diagnostic updates in the WHO 2022 classification of kidney tumours. A major change in this edition is the grouping of renal tumours into broader categories that include "", "", "", as well as adding two categories of "" and "". Novel entities included in the WHO 2022 classification are eosinophilic solid and cystic renal cell carcinoma (ESC RCC), anaplastic lymphoma kinase (-rearranged RCC and (formerly )-mutated RCC. The category of "" includes a group of diverse, unrelated renal tumours that do not fit into other categories. The group of "" reflects recent discoveries in the renal tumour genomics. These molecularly-defined renal entities demonstrate a set of morphologic features reflecting genotype-phenotype relationships. Final diagnosis of such entities rests on phenotypic and immunohistochemical (IHC) correlation, usually associated with IHC surrogate makers that reflect specific genetic abnormalities.
Topics: Humans; Carcinoma, Renal Cell; Kidney; Kidney Neoplasms; World Health Organization
PubMed: 36645398
DOI: 10.32074/1591-951X-818 -
Journal of the National Comprehensive... Jan 2022The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or...
The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology and risk stratification of patients is important in therapy selection. The NCCN Guidelines for Kidney Cancer stratify treatment recommendations by histology; recommendations for first-line treatment of ccRCC are also stratified by risk group. To further guide management of advanced RCC, the NCCN Kidney Cancer Panel has categorized all systemic kidney cancer therapy regimens as "Preferred," "Other Recommended Regimens," or "Useful in Certain Circumstances." This categorization provides guidance on treatment selection by considering the efficacy, safety, evidence, and other factors that play a role in treatment selection. These factors include pre-existing comorbidities, nature of the disease, and in some cases consideration of access to agents. This article summarizes surgical and systemic therapy recommendations for patients with relapsed or stage IV RCC.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Medical Oncology
PubMed: 34991070
DOI: 10.6004/jnccn.2022.0001 -
Oncogene Apr 2020Renal cell carcinoma (RCC) comprises a diverse group of malignancies arising from the nephron. The most prevalent type, clear cell renal cell carcinoma (ccRCC), is... (Review)
Review
Renal cell carcinoma (RCC) comprises a diverse group of malignancies arising from the nephron. The most prevalent type, clear cell renal cell carcinoma (ccRCC), is characterized by genetic mutations in factors governing the hypoxia signaling pathway, resulting in metabolic dysregulation, heightened angiogenesis, intratumoral heterogeneity, and deleterious tumor microenvironmental (TME) crosstalk. Identification of specific genetic variances has led to therapeutic innovation and improved survival for patients with ccRCC. Current barriers to effective long-term therapeutic success highlight the need for continued drug development using improved modeling systems. ccRCC preclinical models can be grouped into three broad categories: cell line, mouse, and 3D models. Yet, the breadth of important unanswered questions in ccRCC research far exceeds the accessibility of model systems capable of carrying them out. Accordingly, we review the strengths, weaknesses, and therapeutic implications of each model system that are relied upon today.
Topics: Animals; Carcinoma, Renal Cell; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Models, Biological; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 32123314
DOI: 10.1038/s41388-020-1234-3 -
Critical Reviews in Oncology/hematology Apr 2021Chromophobe renal cell carcinoma (chRCC) is the third most common type of RCC with distinct biology compared to other kidney cancer subtypes. The heterogeneity between... (Review)
Review
Chromophobe renal cell carcinoma (chRCC) is the third most common type of RCC with distinct biology compared to other kidney cancer subtypes. The heterogeneity between the RCC subtypes is associated with noticeable differences in tumor aggressiveness and risk for the development of metastatic disease. ChRCC is characterized by chromosomal aneuploidy, TP53, PTEN, and mitochondrial gene mutations. Though the therapeutic landscape of clear cell RCC (ccRCC) has significantly evolved over the past decade, limited progress has been seen in chRCC due to its infrequent incidence. In fact, the therapeutic approach for chRCC is often extrapolated from ccRCC treatments or studies that combine several forms of nccRCC subtypes. In the new era of genetic profiling of tumors and targeted therapeutics, this review describes the epidemiology, pathology, molecular characteristics, and current management with ongoing clinical trials for chRCC.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms
PubMed: 33753250
DOI: 10.1016/j.critrevonc.2021.103287 -
Current Treatment Options in Oncology Dec 2023The treatment landscape of renal cell carcinoma (RCC) has evolved significantly over the past three decades. Active surveillance and tumor ablation are alternatives to... (Review)
Review
The treatment landscape of renal cell carcinoma (RCC) has evolved significantly over the past three decades. Active surveillance and tumor ablation are alternatives to extirpative therapy in appropriately selected patients. Stereotactic body radiation therapy (SBRT) is an emerging noninvasive alternative to treat primary RCC tumors. The advent of immune checkpoint inhibitors (ICIs) has greatly improved the overall survival of advanced RCC, and now the ICI-based doublet (dual ICI-ICI doublet; or ICI in combination with a vascular endothelial growth factor tyrosine kinase inhibitor, ICI-TKI doublet) has become the standard frontline therapy. Based on unprecedented outcomes in the metastatic with ICIs, they are also being explored in the neoadjuvant and adjuvant setting for patients with high-risk disease. Adjuvant pembrolizumab has proven efficacy to reduce the risk of RCC recurrence after nephrectomy. Historically considered a radioresistant tumor, SBRT occupies an expanding role to treat RCC with oligometastasis or oligoprogression in combination with systemic therapy. Furthermore, SBRT is being investigated in combination with ICI-doublet in the advanced disease setting. Lastly, given the treatment paradigm is shifting to adopt ICIs at earlier disease course, the prospective studies guiding treatment sequencing in the post-ICI setting is maturing. The effort is ongoing in search of predictive biomarkers to guide optimal treatment option in RCC.
Topics: Humans; Carcinoma, Renal Cell; Prospective Studies; Vascular Endothelial Growth Factor A; Neoplasm Recurrence, Local; Adjuvants, Immunologic; Angiogenesis Inhibitors; Kidney Neoplasms
PubMed: 38153686
DOI: 10.1007/s11864-023-01161-5 -
Clinical and Translational Medicine Jul 2022Kidney cancer is one of the most common solid tumors. The advancement of human kidney cancer research and treatment has been hindered by a lack of research models that...
BACKGROUND
Kidney cancer is one of the most common solid tumors. The advancement of human kidney cancer research and treatment has been hindered by a lack of research models that faithfully recapitulate the diversity of the disease.
METHODS
We established an effective three-dimensional culture system for generating kidney cancer organoids from clinical renal cell carcinoma samples. Renal cell carcinoma (RCC) organoids were characterized by H&E staining, immunofluorescence, whole-exome sequencing, RNA sequencing and single-cell RNA sequencing. The use of RCC organoids in personalized cancer therapy was assessed by testing their responses to treatment drugs and chimeric antigen receptor T cells.
RESULTS
Using this organoid culture system, 33 kidney cancer organoid lines from common kidney cancer subtypes, including clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal cell carcinoma (chRCC), were generated. RCC organoids preserved the histological architectures, mutational landscapes, and transcriptional profile of the parental tumor tissues. Single-cell RNA-sequencing revealed inter- and intra-tumoral heterogeneity in RCC organoids. RCC organoids allowed for in vitro drug screening and provided a tool for assessing the efficacy of chimeric antigen receptor T cells.
CONCLUSIONS
Patient-derived RCC organoids are valuable pre-clinical models for academic research and personalized medicine.
Topics: Carcinoma, Renal Cell; Humans; Kidney; Kidney Neoplasms; Organoids; Receptors, Chimeric Antigen
PubMed: 35802820
DOI: 10.1002/ctm2.970 -
Biochimica Et Biophysica Acta. Reviews... Aug 2021Recent studies have established that tumors can reprogram the pathways involved in nutrient uptake and metabolism to withstand the altered biosynthetic, bioenergetics... (Review)
Review
Recent studies have established that tumors can reprogram the pathways involved in nutrient uptake and metabolism to withstand the altered biosynthetic, bioenergetics and redox requirements of cancer cells. This phenomenon is called metabolic reprogramming, which is promoted by the loss of tumor suppressor genes and activation of oncogenes. Because of alterations and perturbations in multiple metabolic pathways, renal cell carcinoma (RCC) is sometimes termed as a "metabolic disease". The majority of metabolic reprogramming in renal cancer is caused by the inactivation of von Hippel-Lindau (VHL) gene and activation of the Ras-PI3K-AKT-mTOR pathway. Hypoxia-inducible factor (HIF) and Myc are other important players in the metabolic reprogramming of RCC. All types of RCCs are associated with reprogramming of glucose and fatty acid metabolism and the tricarboxylic acid (TCA) cycle. Metabolism of glutamine, tryptophan and arginine is also reprogrammed in renal cancer to favor tumor growth and oncogenesis. Together, understanding these modifications or reprogramming of the metabolic pathways in detail offer ample opportunities for the development of new therapeutic targets and strategies, discovery of biomarkers and identification of effective tumor detection methods.
Topics: Animals; Carcinoma, Renal Cell; Cellular Reprogramming; Disease Progression; Energy Metabolism; Gene Expression Regulation, Neoplastic; Humans; Kidney Neoplasms; Signal Transduction
PubMed: 33965513
DOI: 10.1016/j.bbcan.2021.188559 -
Nature Medicine Jul 2020Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput...
Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) is a highly sensitive assay capable of detecting early-stage tumors. We report accurate classification of patients across all stages of renal cell carcinoma (RCC) in plasma (area under the receiver operating characteristic (AUROC) curve of 0.99) and demonstrate the validity of this assay to identify patients with RCC using urine cell-free DNA (cfDNA; AUROC of 0.86).
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Cell-Free Nucleic Acids; DNA Methylation; Early Detection of Cancer; Epigenome; High-Throughput Nucleotide Sequencing; Humans
PubMed: 32572266
DOI: 10.1038/s41591-020-0933-1