The Experts below are selected from a list of 48504 Experts worldwide ranked by ideXlab platform
Marston W Linehan - One of the best experts on this subject based on the ideXlab platform.
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summary from the first Kidney Cancer research summit september 12 13 2019 a focus on translational research
Journal of the National Cancer Institute, 2021Co-Authors: Toni K Choueiri, Eric Jonasch, Marston W Linehan, Maria I Carlo, Michael B Atkins, Ziad Bakouny, Charles G Drake, Payal Kapur, Bryan Lewis, Michael J MitchellAbstract:Kidney Cancer is one of the 10 most common Cancers both in the United States and worldwide. Until this year, there had not previously been a conference focused on translational studies in the broad and heterogeneous group of Kidney Cancers. Therefore, a group of researchers, clinicians, and patient advocates dedicated to renal cell carcinoma launched the Kidney Cancer Research Summit (KCRS) to spur collaboration and further therapeutic advances in these tumors. This commentary aims to summarize the oral presentations and serve as a record for future iterations of this meeting. The KCRS sessions addressed the tumor microenvironment, novel methods of drug delivery, single cell sequencing strategies, novel immune checkpoint blockade and cellular therapies, predictive biomarkers, and rare variants of Kidney Cancers. In addition, the meeting included 2 sessions to promote scientific mentoring and Kidney Cancer research collaborations. A subsequent KCRS will be planned for the fall of 2020.
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familial Kidney Cancer implications of new syndromes and molecular insights
European Urology, 2019Co-Authors: Maria I Carlo, Marston W Linehan, Gennady Bratslavsky, Ari A Hakimi, Grant D Stewart, James Brugarolas, Yingbei Chen, Eamonn R Maher, Maria J Merino, Kenneth OffitAbstract:Abstract Context Hereditary cases account for about 5% of all cases of renal cell carcinoma (RCC). With advances in next-generation sequencing, several new hereditary syndromes have been described in the last few years. Objective To review and summarise the recent preclinical and clinical literature in hereditary renal Cancer. Evidence acquisition A systematic review of the literature was performed in November 2018 using PubMed and OMIM databases, with an emphasis on Kidney Cancer, genetics and genomics, clinical criteria, and management. Evidence synthesis Several autosomal dominant hereditary RCC syndromes have been described, including those related to germline pathogenic variants in VHL, MET, FH, TSC1/TSC2, FLCN, SDHA/B/C/D, BAP1, CDC73, and MITF. Clinical spectrum of SDH, BAP1, and MITF is still being defined, although these appear to be associated with a lower incidence of RCC. FH and likely BAP1 RCC are associated with more aggressive disease. Preclinical and clinical studies show that using systemic therapy that exploits specific genetic pathways is a promising strategy. Conclusions There are several well-described hereditary RCC syndromes, as well as recently identified ones, for which the full clinical spectrum is yet to be defined. In the new era of precision medicine, identification of these syndromes may play an important role in management and systemic treatment selection. Patient summary This review covers updates in the diagnosis and management of familial Kidney Cancer syndromes. We describe updates in testing and management of the most common syndromes such as von Hippel-Lindau, and hereditary leiomyomatosis and renal cell carcinoma. We also provide insights into recently described familial Kidney Cancer syndromes.
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the metabolic basis of Kidney Cancer
Cancer Discovery, 2019Co-Authors: Marston W Linehan, Laura S Schmidt, Daniel R Crooks, Darmood Wei, Ramaprasad Srinivasan, Martin Lang, Christopher J RickettsAbstract:Kidney Cancer is not a single disease but represents several distinct types of Cancer that have defining histologies and genetic alterations and that follow different clinical courses and have different responses to therapy. Mutation of genes associated with Kidney Cancer, such as VHL, FLCN, TFE3, FH, or SDHB, dysregulates the tumor's responses to changes in oxygen, iron, nutrient, or energy levels. The identification of these varying genetic bases of Kidney Cancer has increased our understanding of the biology of this Cancer, allowing the development of targeted therapies and the appreciation that it is a Cancer driven by metabolic alterations. SIGNIFICANCE: Kidney Cancer is a complex disease composed of different types of Cancer that present with different histologies, clinical courses, genetic changes, and responses to therapy. This review describes the known genetic changes within Kidney Cancer, how they alter tumor metabolism, and how these metabolic changes can be therapeutically targeted.
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genetic predisposition to Kidney Cancer
Seminars in Oncology, 2016Co-Authors: Laura S Schmidt, Marston W LinehanAbstract:Kidney Cancer is not a single disease but is made up of a number of different types of Cancer classified by histology that are disparate in presentation, clinical course, and genetic basis. Studies of families with inherited renal cell carcinoma (RCC) have provided the basis for our understanding of the causative genes and altered metabolic pathways in renal Cancer with different histologies. Von Hippel-Lindau disease was the first renal Cancer disorder with a defined genetic basis. Over the next two decades, the genes responsible for a number of other inherited renal Cancer syndromes including hereditary papillary renal carcinoma, Birt-Hogg-Dube´syndrome, hereditary leiomyomatosis and renal cell carcinoma, and succinate dehydrogenase-associated renal Cancer were identified. Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated Cancer syndrome. Here we summarize the clinical characteristics of and causative genes for these and other inherited RCC syndromes, the pathways that are dysregulated when the inherited genes are mutated, and recommended clinical management of patients with these inherited renal Cancer syndromes.
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detection of an immunogenic herv e envelope with selective expression in clear cell Kidney Cancer
Cancer Research, 2016Co-Authors: Elena Cherkasova, Marston W Linehan, Ramaprasad Srinivasan, Claire Scrivani, Susan Doh, Quinn Weisman, Yoshiyuki Takahashi, Nanae Harashima, Hisayuki Yokoyama, M I LermanAbstract:VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of Kidney Cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E). In this study, we define a transcript encoding the entire envelope gene of HERV-E as expressed selectively in ccRCC tumors, as distinct from normal Kidney tissues or other tumor types. Sequence analysis of this envelope transcript revealed long open reading frames encoding putative surface and transmembrane envelope proteins. Retroviral envelopes are known to be capable of eliciting immunity in humans. Accordingly, we found that HLA-A*0201-restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript stimulated CD8+ T cells which could recognize HLA-A*0201-positive HERV-E-expressing Kidney tumor cells. Overall, our results offer evidence of unique HERV-E envelope peptides presented on the surface of ccRCC cells, offering potentially useful tumor-restricted targets for T cell-based immunotherapy of Kidney Cancer.
Ming Xu - One of the best experts on this subject based on the ideXlab platform.
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retracted twist2 promotes Kidney Cancer cell proliferation and invasion via regulating itga6 and cd44 expression in the ecm receptor interaction pathway
Biomedicine & Pharmacotherapy, 2016Co-Authors: Haojie Zhang, Ruiming Rong, Xin Hu, Lu Sheng, Ming XuAbstract:: Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence proves that Twist2 involves in tumor progression; however, the role of Twist2 in human Kidney Cancer and its underlying mechanisms remain unclear. RT-PCR and Western blot analysis were used to detect the expression of Twist2 in Kidney Cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration and invasion assay was measured by the Cell Count Kit-8 (CCK8), flow cytometry, wound healing and transwell analysis, respectively. Gene set enrichment analysis (GSEA) was used to identify correlation of Twist2 with ECM-Receptor-Interaction pathway. In this report, we show that Twist2 up-regulated in human Kidney Cancer tissues compared with normal Kidney tissues. Twist2 promotes cell proliferation, inhibits cell apoptosis, augments cell migration and invasion in human Kidney Cancer-derived cell in vitro, and promotes tumor growth in vivo. Moreover, we found that knockdown of Twist2 decreased the levels of ITGA6 and CD44 which contribute to cell migration and invasion correlated with ECM-Receptor-Interaction pathway. This result indicates Twist2 may promote migration and invasion of Kidney Cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 involves in Kidney Cancer progression. The identification of the role Twist2 on the migration and invasion of Kidney Cancer provides a potential appropriate treatment after radical nephrectomy to get a better prognosis that reducing recurrence.
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twist2 promotes Kidney Cancer cell proliferation and invasion by regulating itga6 and cd44 expression in the ecm receptor interaction pathway
OncoTargets and Therapy, 2016Co-Authors: Haojie Zhang, Ruiming Rong, Xin Hu, Lu Sheng, Ming XuAbstract:Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence has proven that Twist2 is involved in tumor progression; however, the role of Twist2 in human Kidney Cancer and its underlying mechanisms remain unclear. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of Twist2 in Kidney Cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration, and invasion assay were analyzed using the Cell Count Kit-8, flow cytometry, wound healing, and Transwell analysis, respectively. In this study, we showed that Twist2 was upregulated in human Kidney Cancer tissues compared with normal Kidney tissues. Twist2 promoted cell proliferation, inhibited cell apoptosis, and augmented cell migration and invasion in human Kidney-Cancer-derived cells in vitro. Twist2 also promoted tumor growth in vivo. Moreover, we found that the knockdown of Twist2 decreased the levels of ITGA6 and CD44 expression. This result indicates that Twist2 may promote migration and invasion of Kidney Cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 is involved in Kidney Cancer progression. The identification of the role of Twist2 in the migration and invasion of Kidney Cancer provides a potential appropriate treatment for human Kidney Cancer.
Haojie Zhang - One of the best experts on this subject based on the ideXlab platform.
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retracted twist2 promotes Kidney Cancer cell proliferation and invasion via regulating itga6 and cd44 expression in the ecm receptor interaction pathway
Biomedicine & Pharmacotherapy, 2016Co-Authors: Haojie Zhang, Ruiming Rong, Xin Hu, Lu Sheng, Ming XuAbstract:: Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence proves that Twist2 involves in tumor progression; however, the role of Twist2 in human Kidney Cancer and its underlying mechanisms remain unclear. RT-PCR and Western blot analysis were used to detect the expression of Twist2 in Kidney Cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration and invasion assay was measured by the Cell Count Kit-8 (CCK8), flow cytometry, wound healing and transwell analysis, respectively. Gene set enrichment analysis (GSEA) was used to identify correlation of Twist2 with ECM-Receptor-Interaction pathway. In this report, we show that Twist2 up-regulated in human Kidney Cancer tissues compared with normal Kidney tissues. Twist2 promotes cell proliferation, inhibits cell apoptosis, augments cell migration and invasion in human Kidney Cancer-derived cell in vitro, and promotes tumor growth in vivo. Moreover, we found that knockdown of Twist2 decreased the levels of ITGA6 and CD44 which contribute to cell migration and invasion correlated with ECM-Receptor-Interaction pathway. This result indicates Twist2 may promote migration and invasion of Kidney Cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 involves in Kidney Cancer progression. The identification of the role Twist2 on the migration and invasion of Kidney Cancer provides a potential appropriate treatment after radical nephrectomy to get a better prognosis that reducing recurrence.
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twist2 promotes Kidney Cancer cell proliferation and invasion by regulating itga6 and cd44 expression in the ecm receptor interaction pathway
OncoTargets and Therapy, 2016Co-Authors: Haojie Zhang, Ruiming Rong, Xin Hu, Lu Sheng, Ming XuAbstract:Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence has proven that Twist2 is involved in tumor progression; however, the role of Twist2 in human Kidney Cancer and its underlying mechanisms remain unclear. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of Twist2 in Kidney Cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration, and invasion assay were analyzed using the Cell Count Kit-8, flow cytometry, wound healing, and Transwell analysis, respectively. In this study, we showed that Twist2 was upregulated in human Kidney Cancer tissues compared with normal Kidney tissues. Twist2 promoted cell proliferation, inhibited cell apoptosis, and augmented cell migration and invasion in human Kidney-Cancer-derived cells in vitro. Twist2 also promoted tumor growth in vivo. Moreover, we found that the knockdown of Twist2 decreased the levels of ITGA6 and CD44 expression. This result indicates that Twist2 may promote migration and invasion of Kidney Cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 is involved in Kidney Cancer progression. The identification of the role of Twist2 in the migration and invasion of Kidney Cancer provides a potential appropriate treatment for human Kidney Cancer.
Ramaprasad Srinivasan - One of the best experts on this subject based on the ideXlab platform.
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the metabolic basis of Kidney Cancer
Cancer Discovery, 2019Co-Authors: Marston W Linehan, Laura S Schmidt, Daniel R Crooks, Darmood Wei, Ramaprasad Srinivasan, Martin Lang, Christopher J RickettsAbstract:Kidney Cancer is not a single disease but represents several distinct types of Cancer that have defining histologies and genetic alterations and that follow different clinical courses and have different responses to therapy. Mutation of genes associated with Kidney Cancer, such as VHL, FLCN, TFE3, FH, or SDHB, dysregulates the tumor's responses to changes in oxygen, iron, nutrient, or energy levels. The identification of these varying genetic bases of Kidney Cancer has increased our understanding of the biology of this Cancer, allowing the development of targeted therapies and the appreciation that it is a Cancer driven by metabolic alterations. SIGNIFICANCE: Kidney Cancer is a complex disease composed of different types of Cancer that present with different histologies, clinical courses, genetic changes, and responses to therapy. This review describes the known genetic changes within Kidney Cancer, how they alter tumor metabolism, and how these metabolic changes can be therapeutically targeted.
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detection of an immunogenic herv e envelope with selective expression in clear cell Kidney Cancer
Cancer Research, 2016Co-Authors: Elena Cherkasova, Marston W Linehan, Ramaprasad Srinivasan, Claire Scrivani, Susan Doh, Quinn Weisman, Yoshiyuki Takahashi, Nanae Harashima, Hisayuki Yokoyama, M I LermanAbstract:VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of Kidney Cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E). In this study, we define a transcript encoding the entire envelope gene of HERV-E as expressed selectively in ccRCC tumors, as distinct from normal Kidney tissues or other tumor types. Sequence analysis of this envelope transcript revealed long open reading frames encoding putative surface and transmembrane envelope proteins. Retroviral envelopes are known to be capable of eliciting immunity in humans. Accordingly, we found that HLA-A*0201-restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript stimulated CD8+ T cells which could recognize HLA-A*0201-positive HERV-E-expressing Kidney tumor cells. Overall, our results offer evidence of unique HERV-E envelope peptides presented on the surface of ccRCC cells, offering potentially useful tumor-restricted targets for T cell-based immunotherapy of Kidney Cancer.
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detection of an immunogenic herv e envelope with selective expression in clear cell Kidney Cancer
Cancer Research, 2016Co-Authors: Elena Cherkasova, Marston W Linehan, Ramaprasad Srinivasan, Claire Scrivani, Susan Doh, Quinn Weisman, Yoshiyuki Takahashi, Nanae Harashima, Hisayuki Yokoyama, M I LermanAbstract:VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of Kidney Cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E). In this study, we define a transcript encoding the entire envelope gene of HERV-E as expressed selectively in ccRCC tumors, as distinct from normal Kidney tissues or other tumor types. Sequence analysis of this envelope transcript revealed long open reading frames encoding putative surface and transmembrane envelope proteins. Retroviral envelopes are known to be capable of eliciting immunity in humans. Accordingly, we found that HLA-A*0201-restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript-stimulated CD8(+) T cells, which could recognize HLA-A*0201-positive HERV-E-expressing Kidney tumor cells. Overall, our results offer evidence of unique HERV-E envelope peptides presented on the surface of ccRCC cells, offering potentially useful tumor-restricted targets for T-cell-based immunotherapy of Kidney Cancer. Cancer Res; 76(8); 2177-85. ©2016 AACR.
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metabolism and oxidative stress response pathways in Kidney Cancer a tale of chance and necessity
American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting, 2015Co-Authors: Carole Sourbier, Ramaprasad Srinivasan, Marston W LinehanAbstract:Over 270,000 patients are affected with Kidney Cancer worldwide and 120,000 died from this disease in 2014. Over the last few decades, important progress has been made in our understanding of the g...
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the genetic basis of Kidney Cancer a metabolic disease
Nature Reviews Urology, 2010Co-Authors: Marston W Linehan, Ramaprasad Srinivasan, Laura S SchmidtAbstract:Kidney Cancer is not a single disease but comprises a number of different types of Cancer that occur in the Kidney, each caused by a different gene with a different histology and clinical course that responds differently to therapy. Each of the seven known Kidney Cancer genes, VHL, MET, FLCN, TSC1, TSC2, FH and SDH, is involved in pathways that respond to metabolic stress or nutrient stimulation. The VHL protein is a component of the oxygen and iron sensing pathway that regulates hypoxia-inducible factor (HIF) levels in the cell. HGF-MET signaling affects the LKB1-AMPK energy sensing cascade. The FLCN-FNIP1-FNIP2 complex binds AMPK and, therefore, might interact with the cellular energy and nutrient sensing pathways AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR. TSC1-TSC2 is downstream of AMPK and negatively regulates mTOR in response to cellular energy deficit. FH and SDH have a central role in the mitochondrial tricarboxylic acid cycle, which is coupled to energy production through oxidative phosphorylation. Mutations in each of these Kidney Cancer genes result in dysregulation of metabolic pathways involved in oxygen, iron, energy or nutrient sensing, suggesting that Kidney Cancer is a disease of cell metabolism. Targeting the fundamental metabolic abnormalities in Kidney Cancer provides a unique opportunity for the development of more-effective forms of therapy for this disease.
Toni K Choueiri - One of the best experts on this subject based on the ideXlab platform.
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summary from the first Kidney Cancer research summit september 12 13 2019 a focus on translational research
Journal of the National Cancer Institute, 2021Co-Authors: Toni K Choueiri, Eric Jonasch, Marston W Linehan, Maria I Carlo, Michael B Atkins, Ziad Bakouny, Charles G Drake, Payal Kapur, Bryan Lewis, Michael J MitchellAbstract:Kidney Cancer is one of the 10 most common Cancers both in the United States and worldwide. Until this year, there had not previously been a conference focused on translational studies in the broad and heterogeneous group of Kidney Cancers. Therefore, a group of researchers, clinicians, and patient advocates dedicated to renal cell carcinoma launched the Kidney Cancer Research Summit (KCRS) to spur collaboration and further therapeutic advances in these tumors. This commentary aims to summarize the oral presentations and serve as a record for future iterations of this meeting. The KCRS sessions addressed the tumor microenvironment, novel methods of drug delivery, single cell sequencing strategies, novel immune checkpoint blockade and cellular therapies, predictive biomarkers, and rare variants of Kidney Cancers. In addition, the meeting included 2 sessions to promote scientific mentoring and Kidney Cancer research collaborations. A subsequent KCRS will be planned for the fall of 2020.
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Kidney Cancer version 1 2021 featured updates to the nccn guidelines
Journal of The National Comprehensive Cancer Network, 2020Co-Authors: Robert J Motzer, Eric Jonasch, Neeraj Agarwal, Toni K Choueiri, Maria I Carlo, Shawna L Boyle, Brandon Manley, Ajjai Alva, Katy Beckermann, Brian A CostelloAbstract:The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to certain systemic therapy recommendations for patients with relapsed or stage IV RCC. They also discuss the addition of a new section to the guidelines that identifies and describes the most common hereditary RCC syndromes and provides recommendations for genetic testing, surveillance, and/or treatment options for patients who are suspected or confirmed to have one of these syndromes.
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Kidney Cancer version 2 2017 nccn clinical practice guidelines in oncology
Journal of The National Comprehensive Cancer Network, 2017Co-Authors: Robert J Motzer, Eric Jonasch, Neeraj Agarwal, Sam B Bhayani, William P Bro, Sam S Chang, Toni K Choueiri, Brian A Costello, Ithaar H Derweesh, Mayer FishmanAbstract:The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.
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Kidney Cancer version 3 2015 featured updates to the nccn guidelines
Journal of The National Comprehensive Cancer Network, 2015Co-Authors: Robert J Motzer, Eric Jonasch, Neeraj Agarwal, Sam B Bhayani, Sam S Chang, Toni K Choueiri, Brian A Costello, Clair J Beard, Graeme B Bolger, Ithaar H DerweeshAbstract:The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These NCCN Guidelines Insights highlight the recent updates/changes in these guidelines, and updates include axitinib as first-line treatment option for patients with clear cell renal carcinoma, new data to support pazopanib as subsequent therapy for patients with clear cell carcinoma after first-line treatment with another tyrosine kinase inhibitor, and guidelines for follow-up of patients with renal cell carcinoma.
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Kidney Cancer version 2 2014
Journal of The National Comprehensive Cancer Network, 2014Co-Authors: Robert J Motzer, Eric Jonasch, Neeraj Agarwal, Sam B Bhayani, Sam S Chang, Toni K Choueiri, Ithaar H Derweesh, Clair J Beard, Graeme B Bolger, Shilpa GuptaAbstract:Abstract These NCCN Guidelines Insights highlight treatment recommendations and updates specific to the management of patients with advanced non-clear cell carcinoma included in the 2014 version of the NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer.
