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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 -
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 -
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 -
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 -
The Journal of Experimental Medicine Oct 2018Chris Boshoff, Senior Vice President of Immuno-Oncology, Translational and Early Development at Pfizer, and colleagues Samra Turajlic and Charles Swanton from the...
Chris Boshoff, Senior Vice President of Immuno-Oncology, Translational and Early Development at Pfizer, and colleagues Samra Turajlic and Charles Swanton from the Francis Crick Institute and University College London give us their personal point of view on new insights and future therapeutic approaches for renal cancer.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Kidney Tubules, Proximal; Prognosis
PubMed: 30217855
DOI: 10.1084/jem.20181617 -
Current Opinion in Urology Jul 2022Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype and represents 15-20% of all RCC. Classification of pRCC is changing because novel... (Review)
Review
PURPOSE OF THE REVIEW
Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype and represents 15-20% of all RCC. Classification of pRCC is changing because novel tumour entities have been discovered in the last years. In this review, we summarise recent studies relevant for the understanding of the molecular complexity and the broader differential diagnosis of pRCC.
RECENT FINDINGS
It has been 25 years ago, that pRCC was morphologically subdivided into type 1 and type 2. Recently described tumour entities in the 2022 WHO classification challenged this concept and allow a new view on the molecular background in pRCC. Biphasic hyalinizing psammomatous RCC and papillary renal neoplasm with reversed polarity are emerging tumour entities derived from the new concept of molecularly defined RCC subtypes. Immune checkpoint inhibition and tyrosine kinase inhibitors have been introduced as the new backbone in the first-line treatment of advanced pRCCs. To identify novel targeted treatments for patients with pRCC it is crucial to investigate the specific molecular background of pRCC considering emerging pRCC subtypes.
SUMMARY
In the future, a deeper understanding of the correlation between molecular aberrations and new pRCC subtypes may improve the classification of pRCC patients and could reveal potential predictive biomarkers for each subgroup.
Topics: Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney Neoplasms
PubMed: 35674688
DOI: 10.1097/MOU.0000000000001000 -
Journal of Experimental & Clinical... May 2023Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Large-scale metabolomic data have associated metabolic alterations with the...
BACKGROUND
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Large-scale metabolomic data have associated metabolic alterations with the pathogenesis and progression of renal carcinoma and have correlated mitochondrial activity with poor survival in a subset of patients. The aim of this study was to determine whether targeting mitochondria-lysosome interaction could be a novel therapeutic approach using patient-derived organoids as avatar for drug response.
METHODS
RNAseq data analysis and immunohistochemistry were used to show overexpression of Purinergic receptor 4 (P2XR4) in clear cell carcinomas. Seahorse experiments, immunofluorescence and fluorescence cell sorting were used to demonstrate that P2XR4 regulates mitochondrial activity and the balance of radical oxygen species. Pharmacological inhibitors and genetic silencing promoted lysosomal damage, calcium overload in mitochondria and cell death via both necrosis and apoptosis. Finally, we established patient-derived organoids and murine xenograft models to investigate the antitumor effect of P2XR4 inhibition using imaging drug screening, viability assay and immunohistochemistry.
RESULTS
Our data suggest that oxo-phosphorylation is the main source of tumor-derived ATP in a subset of ccRCC cells expressing P2XR4, which exerts a critical impact on tumor energy metabolism and mitochondrial activity. Prolonged mitochondrial failure induced by pharmacological inhibition or P2XR4 silencing was associated with increased oxygen radical species, changes in mitochondrial permeability (i.e., opening of the transition pore complex, dissipation of membrane potential, and calcium overload). Interestingly, higher mitochondrial activity in patient derived organoids was associated with greater sensitivity to P2XR4 inhibition and tumor reduction in a xenograft model.
CONCLUSION
Overall, our results suggest that the perturbed balance between lysosomal integrity and mitochondrial activity induced by P2XR4 inhibition may represent a new therapeutic strategy for a subset of patients with renal carcinoma and that individualized organoids may be help to predict drug efficacy.
Topics: Humans; Animals; Mice; Carcinoma, Renal Cell; Receptors, Purinergic P2X4; Calcium; Kidney Neoplasms; Mitochondria; Cell Line, Tumor
PubMed: 37231503
DOI: 10.1186/s13046-023-02713-1 -
International Journal of Molecular... Jul 2019A significantly increased level of the reactive oxygen species (ROS) scavenger glutathione (GSH) has been identified as a hallmark of renal cell carcinoma (RCC). The... (Review)
Review
A significantly increased level of the reactive oxygen species (ROS) scavenger glutathione (GSH) has been identified as a hallmark of renal cell carcinoma (RCC). The proposed mechanism for increased GSH levels is to counteract damaging ROS to sustain the viability and growth of the malignancy. Here, we review the current knowledge about the three main RCC subtypes, namely clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC), at the genetic, transcript, protein, and metabolite level and highlight their mutual influence on GSH metabolism. A further discussion addresses the question of how the manipulation of GSH levels can be exploited as a potential treatment strategy for RCC.
Topics: Animals; Biomarkers, Tumor; Carcinoma, Renal Cell; Disease Models, Animal; Disease Progression; Glutathione; Humans; Kidney Neoplasms; Metabolic Networks and Pathways; Molecular Targeted Therapy; Oxidative Stress; Reactive Oxygen Species; Tumor Microenvironment
PubMed: 31357507
DOI: 10.3390/ijms20153672 -
Archivos Espanoles de Urologia Jan 2020There is still limited knowledgeabout surveillance and optimal management for patientswith recurrent chromophobe renal cell carcinoma. OBJECTIVE: Describe our...
INTRODUCTION
There is still limited knowledgeabout surveillance and optimal management for patientswith recurrent chromophobe renal cell carcinoma. OBJECTIVE: Describe our experience in the diagnosis andmanagement in recurrent chromophobe renal cell carcinoma.
MATERIAL AND METHOD
Review of medical records ofpatients with chromophobe renal cell carcinoma, selectingthose cases that developed recurrence.
RESULTS
Of the 23 patients, 4 developed recurrence andwere the subjects of our analysis. The mean age was 61.5years. Surgical treatment of primary renal tumor consistedof three radical nephrectomies and one partial nephrectomy.The mean time from nephrectomy to disease recurrencewas 6.7 years. One patient had recurrence in the retrovesicalarea, another in bone, and the two others in theretroperitoneum. The treatment for retrovesical recurrencewas an incomplete metastasectomy followed by temsirolimusand subsequent removal of the residual mass, stayingstable. The other three cases were unresectable surgicallyand received sunitinib. One patient now has a stable diseaseand the two others died. CONCLUSIONS: Chromophobe renal cell carcinomashowed a greater tendency to metastasize, so requires asurveillance protocol based on the risk of recurrence.
Topics: Carcinoma, Renal Cell; Humans; Kidney; Kidney Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Nephrectomy; Retrospective Studies
PubMed: 31950927
DOI: No ID Found