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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 -
American Family Physician Feb 2019Kidney cancer is one of the 10 most common cancers in the United States with 90% being attributed to renal cell carcinoma. Men, especially black men, are more likely to... (Review)
Review
Kidney cancer is one of the 10 most common cancers in the United States with 90% being attributed to renal cell carcinoma. Men, especially black men, are more likely to be affected than women. Renal masses, either cystic or solid, are best detected with contrast-enhanced, triple-phase computed tomography. Renal tumors are often detected incidentally during a computed tomography scan of the abdomen or chest that was ordered for unrelated symptoms. Hematuria serves as a warning sign that necessitates further evaluation and imaging leading to a diagnosis and treatment plan. Treatment options include active surveillance, ablation, nephron-sparing tumor excision, nephrectomy, and systemic treatment. Predictors of a poor prognosis include poor functional status and metastasis. In recent years new therapies have improved the prognosis for patients with metastatic disease. The family physician should be aware of risk factors (e.g., hypertension, tobacco use, exposure to trichloroethylene, familial syndromes) and lifestyle and dietary modifications that may reduce risk.
Topics: Carcinoma, Renal Cell; Diagnosis, Differential; Female; Hematuria; Humans; Incidental Findings; Kidney Neoplasms; Male; Neoplasm Staging; Tomography, X-Ray Computed
PubMed: 30702258
DOI: No ID Found -
Lancet (London, England) Mar 2009Considerable progress has been made in the treatment of patients with renal cell carcinoma, with innovative surgical and systemic strategies revolutionising the... (Review)
Review
Considerable progress has been made in the treatment of patients with renal cell carcinoma, with innovative surgical and systemic strategies revolutionising the management of this disease. In localised disease, partial nephrectomy for small tumours and radical nephrectomy for large tumours continue to be the gold-standard treatments, with emphasis on approaches that have reduced invasiveness and preserve renal function. Additionally, cytoreductive nephrectomy is often indicated before the start of systemic treatment in patients with metastatic disease as part of integrated management strategy. The effectiveness of immunotherapy, although previously widely used for treatment of metastatic renal cell carcinoma, is still controversial, and is mainly reserved for patients with good prognostic factors. Development of treatments that have specific targets in relevant biological pathways has been the main advance in treatment. Targeted drugs, including inhibitors of the vascular endothelial growth factor and mammalian target of rapamycin pathways, have shown robust effectiveness and offer new therapeutic options for the patients with metastatic disease.
Topics: Carcinoma, Renal Cell; Female; Humans; Kidney Neoplasms; Male
PubMed: 19269025
DOI: 10.1016/S0140-6736(09)60229-4 -
Biomedical Papers of the Medical... Jun 2016The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or... (Review)
Review
BACKGROUND AND AIMS
The global incidence of renal cell cancer is increasing annually and the causes are multifactorial. Early diagnosis and successful urological procedures with partial or total nephrectomy can be life-saving. However, only up to 10% of RCC patients present with characteristic clinical symptoms. Over 60% are detected incidentally in routine ultrasound examination. The question of screening and preventive measures greatly depends on the cause of the tumor development. For the latter reason, this review focuses on etiology, pathophysiology and risk factors for renal neoplasm.
METHODS
A literature search using the databases Medscape, Pubmed, UpToDate and EBSCO from 1945 to 2015.
RESULTS AND CONCLUSIONS
Genetic predisposition/hereditary disorders, obesity, smoking, various nephrotoxic industrial chemicals, drugs and natural/manmade radioactivity all contribute and enviromental risks are a serious concern in terms of prevention and the need to screen populations at risk. Apropos treatment, current oncological research is directed to blocking cancer cell division and inhibiting angiogenesis based on a knowledge of molecular pathways.
Topics: Carcinogenesis; Carcinoma, Renal Cell; Genetic Predisposition to Disease; Humans; Kidney Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Radiation Exposure; Risk Factors; Uranium Compounds
PubMed: 26558360
DOI: 10.5507/bp.2015.050 -
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 -
BMJ (Clinical Research Ed.) Nov 2014The treatment of renal cell carcinoma (RCC) has changed greatly over the past 15 years. Progress in the surgical management of the primary tumor and increased... (Review)
Review
The treatment of renal cell carcinoma (RCC) has changed greatly over the past 15 years. Progress in the surgical management of the primary tumor and increased understanding of the molecular biology and genomics of the disease have led to the development of new therapeutic agents. The management of the primary tumor has changed owing to the realization that clean margins around the primary lesion are sufficient to prevent local recurrence, as well as the development of more sophisticated tools and techniques that increase the safety of partial nephrectomy. The management of advanced disease has altered even more dramatically as a result of new agents that target the tumor vasculature or that attenuate the activation of intracellular oncogenic pathways. This review summarizes data from prospective randomized phase III studies on the surgical management and systemic treatment of RCC, and provides an up to date summary of the histology, genomics, staging, and prognosis of RCC. It describes the management of the primary tumor and offers an overview of systemic agents that form the mainstay of treatment for advanced disease. The review concludes with an introduction to the exciting new class of immunomodulatory agents that are currently in clinical trials and may form the basis of a new therapeutic approach for patients with advanced RCC.
Topics: Antineoplastic Agents; Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Genomics; Humans; Incidence; Kidney Neoplasms; Mutation; Neoplasm Metastasis; Neoplasm Staging; Prevalence; Prognosis
PubMed: 25385470
DOI: 10.1136/bmj.g4797 -
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 -
Journal of Experimental & Clinical... Aug 2021The incidence of renal cell carcinoma (RCC) is increasing worldwide with an approximate 20% mortality rate. The challenge in RCC is the therapy-resistance. Cancer... (Review)
Review
The incidence of renal cell carcinoma (RCC) is increasing worldwide with an approximate 20% mortality rate. The challenge in RCC is the therapy-resistance. Cancer resistance to treatment employs multiple mechanisms due to cancer heterogeneity with multiple genetic and epigenetic alterations. These changes include aberrant overexpression of (1) anticancer cell death proteins (e.g., survivin/BIRC5), (2) DNA repair regulators (e.g., ERCC6) and (3) efflux pump proteins (e.g., ABCG2/BCRP); mutations and/or deregulation of key (4) oncogenes (e.g., MDM2, KRAS) and/or (5) tumor suppressor genes (e.g., TP5/p53); and (6) deregulation of redox-sensitive regulators (e.g., HIF, NRF2). Foci of tumor cells that have these genetic alterations and/or deregulation possess survival advantages and are selected for survival during treatment. We will review the significance of survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, TP5/p53, KRAS and AKT in treatment resistance as the potential therapeutic biomarkers and/or targets in RCC in parallel with our analized RCC-relevant TCGA genetic results from each of these gene/protein molecules. We then present our data to show the anticancer drug FL118 modulation of these protein targets and RCC cell/tumor growth. Finally, we include additional data to show a promising FL118 analogue (FL496) for treating the specialized type 2 papillary RCC.
Topics: Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Kidney Neoplasms
PubMed: 34384473
DOI: 10.1186/s13046-021-02026-1 -
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