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Cabozantinib and renal

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https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#1
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28417541/clinical-efficacy-of-cabozantinib-in-two-pediatric-patients-with-recurrent-renal-cell-carcinoma
#2
Mary Frances Wedekind, Mark Ranalli, Nilay Shah
Advanced-stage renal cell carcinoma (RCC) carries a dismal prognosis for pediatric patients with few studied therapeutic options. Cabozantinib is a small molecule tyrosine kinase inhibitor against the oncoprotein MET. It is currently approved by the U.S. Food and Drug administration for second-line treatment of RCC in adults. There is no published data on its use in children with RCC. We report here two pediatric patients with recurrent metastatic RCC whose tumors expressed MET and were treated with cabozantinib...
April 18, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28413127/evolution-of-circulating-tumor-dna-profile-from-first-line-to-subsequent-therapy-in-metastatic-renal-cell-carcinoma
#3
Sumanta K Pal, Guru Sonpavde, Neeraj Agarwal, Nicholas J Vogelzang, Sandy Srinivas, Naomi B Haas, Sabina Signoretti, Bradley A McGregor, Jeremy Jones, Richard B Lanman, Kimberly C Banks, Toni K Choueiri
BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) typically entails mechanistically distinct agents across the first- and second-line setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. Circulating tumor DNA (ctDNA) is a platform to noninvasively ascertain temporal changes in genomic profile. OBJECTIVE: To assess the ctDNA profile in a large cohort of mRCC patients, and to assess changes across patients receiving first-line and later lines of therapy...
April 13, 2017: European Urology
https://www.readbyqxmd.com/read/28403496/-interdisciplinary-recommendations-for-the-treatment-of-metastatic-renal-cell-carcinoma
#4
Kurt Miller, Lothar Bergmann, Christian Doehn, Jürgen Gschwend, Ulrich Keilholz
Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure...
February 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#5
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28303494/current-management-strategy-for-metastatic-renal-cell-carcinoma-and-future-directions
#6
REVIEW
Hussein Merza, Marijo Bilusic
PURPOSE OF REVIEW: Major strides have been made in the treatment of kidney cancer in the last several years with checkpoint immunotherapies and novel targeted agents. This manuscript will review current treatment strategies for metastatic renal cell carcinoma and will discuss future directions. RECENT FINDINGS: Most recently, several new drugs including nivolumab, cabozantinib, and a combination of lenvatinib and everolimus have demonstrated acceptable toxicity and significantly improved overall survival, but evidence-based guidelines for sequencing of the approved treatment options and treatment selection based on biomarkers are still missing...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28286925/cabozantinib-for-renal-cell-carcinoma-current-and-future-paradigms
#7
REVIEW
Ahmed Abdelaziz, Ulka Vaishampayan
Cabozantinib was approved by the FDA in April 2016 for the treatment of advanced renal cancer, pretreated with at least one prior antiangiogenic therapy. This is the first agent in the therapy of kidney cancer to show a statistically significant improvement in all three endpoints of clinical efficacy, response rate, progression free survival, and overall survival (OS), in a phase III randomized trial. The reporting of METEOR coincided with that of the Checkmate 025 study which randomized similarly eligible patients to receive nivolumab or everolimus 10 mg daily...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28276433/renal-cell-carcinoma
#8
REVIEW
James J Hsieh, Mark P Purdue, Sabina Signoretti, Charles Swanton, Laurence Albiges, Manuela Schmidinger, Daniel Y Heng, James Larkin, Vincenzo Ficarra
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance...
March 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28252459/renal-cell-carcinoma-molecular-characterization-and-evolving-treatment-paradigms
#9
Mark W Ball, Eric A Singer, Ramaprasad Srinivasan
PURPOSE OF REVIEW: The treatment landscape of advanced renal cell carcinoma (RCC) continues to shift as both new targeted therapies and immunotherapies show efficacy in treating the disease. Contemporary insights into the molecular characterization of RCC are likely to fuel the development of additional therapies. This review summarizes recent advancements in the biologic characterization of RCC and discusses newly approved therapies and ongoing studies in the treatment of advanced RCC...
March 1, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28247252/cabozantinib-an-active-novel-multikinase-inhibitor-in-renal-cell-carcinoma
#10
REVIEW
Nizar M Tannir, Gisela Schwab, Viktor Grünwald
Clear cell renal cell carcinoma (RCC) is characterized by inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL loss drives tumor angiogenesis and accounts for the clinical activity of VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), the first-line standard of care for advanced RCC. Within the last year, three new second-line treatments have received FDA approval for use after anti-angiogenic therapy: the immune checkpoint inhibitor nivolumab, the TKI cabozantinib, and the combination of the TKI lenvatinib and the mTOR inhibitor everolimus...
February 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28224821/lenvatinib-for-use-in-combination-with-everolimus-for-the-treatment-of-patients-with-advanced-renal-cell-carcinoma-following-one-prior-anti-angiogenic-therapy
#11
REVIEW
Aine O'Reilly, James Larkin
In patients with mRCC options for second line therapies, following progression on anti-angiogenic agents, that demonstrate a survival advantage in clinical trials have been limited. Recently a number of agents have demonstrated efficacy in this setting. Here in we profile one such therapy, the combination of lenvatinib and everolimus, and discuss the expanded options for therapy available in this setting. Areas covered: In this review, we discuss current algorithms for treatment of mRCC in both the first-line and second-line setting...
March 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28223547/cabozantinib-targets-bone-microenvironment-modulating-human-osteoclast-and-osteoblast-functions
#12
Marco Fioramonti, Daniele Santini, Michele Iuliani, Giulia Ribelli, Paolo Manca, Nicola Papapietro, Filippo Spiezia, Bruno Vincenzi, Vincenzo Denaro, Antonio Russo, Giuseppe Tonini, Francesco Pantano
Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28199818/cabozantinib-versus-sunitinib-as-initial-targeted-therapy-for-patients-with-metastatic-renal-cell-carcinoma-of-poor-or-intermediate-risk-the-alliance-a031203-cabosun-trial
#13
Toni K Choueiri, Susan Halabi, Ben L Sanford, Olwen Hahn, M Dror Michaelson, Meghara K Walsh, Darren R Feldman, Thomas Olencki, Joel Picus, Eric J Small, Shaker Dakhil, Daniel J George, Michael J Morris
Purpose Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC. Patients and Methods Eligible patients had untreated clear cell mRCC and Eastern Cooperative Oncology Group performance status of 0 to 2 and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria...
February 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28153029/new-treatment-options-for-metastatic-renal-cell-carcinoma-with-prior-anti-angiogenesis-therapy
#14
REVIEW
Kevin Zarrabi, Chunhui Fang, Shenhong Wu
Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus...
February 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28152689/comparative-effectiveness-research-in-renal-cell-carcinoma-lenvatinib-with-everolimus-as-a-potential-new-treatment-option
#15
Corey Pelletier, Unnati Majethia, Anna Forsythe
27 Background: Renal cell carcinoma (RCC) is the most common type of kidney cancer and represents about 90% of all kidney cancers. As comprehensive comparison of the efficacy associated with mRCC treatments is not available, the goal of this research was to provide a comparative effectiveness analysis including overall survival (OS) and progression free survival (PFS) for first and second line treatments. METHODS: Systematic literature review yielded the following randomized active-controlled studies: lenvatinib + everolimus (LEN+EVE) versus everolimus (EVE), axinitib (AXI) versus sorafenib (SOR), cabozantinib (CAB) versus EVE, nivolumab (NIV) versus EVE, and pazopanib (PAZ) versus sunitinib (SUN)...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28131876/modulating-the-function-of-atp-binding-cassette-subfamily-g-member-2-abcg2-with-inhibitor-cabozantinib
#16
Guan-Nan Zhang, Yun-Kai Zhang, Yi-Jun Wang, Anna Maria Barbuti, Xi-Jun Zhu, Xin-Yue Yu, Ai-Wen Wen, John N D Wurpel, Zhe-Sheng Chen
Cabozantinib (XL184) is a small molecule tyrosine kinase receptor inhibitor, which targets c-Met and VEGFR2. Cabozantinib has been approved by the Food and Drug Administration to treat advanced medullary thyroid cancer and renal cell carcinoma. In the present study, we evaluated the ability of cabozantinib to modulate the function of the ATP-binding cassette subfamily G member 2 (ABCG2) by sensitizing cells that are resistant to ABCG2 substrate antineoplastic drugs. We used a drug-selected resistant cell line H460/MX20 and three ABCG2 stable transfected cell lines ABCG2-482-R2, ABCG2-482-G2, and ABCG2-482-T7, which overexpress ABCG2...
May 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28105863/the-role-of-mtor-inhibition-as-second-line-therapy-in-metastatic-renal-carcinoma-clinical-evidence-and-current-challenges
#17
José Luis González-Larriba, Pablo Maroto, Ignacio Durán, Julio Lambea, Luis Flores, Daniel Castellano, The Changing Group
Sequential treatment with targeted agents is the standard of care for patients with metastatic renal cell carcinoma (mRCC). Although first-line therapy with tyrosine kinase inhibitors (TKIs) is recommended for most patients, eventually all patients become resistant to them. Therefore, optimal selection of second-line therapy is crucial. Areas covered: We have reviewed the recent literature through pubmed search and recent congress presentations to briefly describe the clinical evidence for mTOR inhibition as a valid strategy in the treatment of mRCC after progression during anti-VEGFR therapy...
March 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28096936/treatment-options-in-advanced-renal-cell-carcinoma-after-first-line-treatment-with-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors
#18
REVIEW
Naveen S Basappa
Targeted therapy for metastatic renal cell carcinoma (mRCC) was introduced a decade ago and since then, a number of therapeutic options have been developed. Vascular endothelial growth factor-targeted therapy is the widely accepted first-line option for mRCC. After progression, treatment in the second-line setting has typically been with either axitinib or everolimus. However, with the advent of several new agents demonstrating efficacy in the second-line setting, including nivolumab, cabozantinib, and the combination of lenvatinib and everolimus, the treatment paradigm has shifted toward these novel therapies with improved patient outcomes...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28078236/cabozantinib-in-advanced-renal-cell-carcinoma-a-meteor-impact-on-clinical-practice
#19
EDITORIAL
Paolo Grassi, Elena Verzoni, Alessia Mennitto, Giuseppe Procopio
No abstract text is available yet for this article.
December 2016: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28062674/mixed-results-for-sunitinib-in-renal-cancer
#20
(no author information available yet)
Two studies presented at the European Society for Medical Oncology 2016 Congress evaluated sunitinib in patients with renal cell carcinomas. The first found that the drug prevents recurrence in patients who have had their cancerous kidney removed. The second study suggested that cabozantinib, approved for use as a second-line therapy, works better than sunitinib as a first-line treatment in patients with metastatic renal cell carcinoma.
January 2017: Cancer Discovery
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