scholarly journals Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandro Conti ◽  
Matteo Santoni ◽  
Consuelo Amantini ◽  
Luciano Burattini ◽  
Rossana Berardi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Angiogenesis ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Phosphatidylinositol 3 Kinase ◽  
Von Hippel Lindau ◽  
Angiogenesis Process ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases,α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3′-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents.

Long-lasting response with polycythemia to third-line axitinib treatment in metastatic renal cell carcinoma: Very rare case presentation

2018 ◽  
Vol 25 (6) ◽  
pp. 1512-1515 ◽  
Author(s):  
Ozgecan Dulgar ◽  
Ibrahim Cil ◽  
Alisan Zirtiloglu ◽  
Deniz Tural
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Hemoglobin Level ◽  
Vascular Endothelial ◽  
Von Hippel Lindau ◽  
Third Line ◽  
Endothelial Growth Factor

Introduction Clear cell renal cell carcinoma is characterized by mutation or inactivation of Von Hippel-Lindau suppressor gene. The mutation of Von Hippel-Lindau mechanism is associated with the upregulation of the hypoxia-inducible factor protein, inducing the overexpression of proteins including erythropoietin and vascular endothelial growth factor. Vascular endothelial growth factor receptor-targeted tyrosine kinase inhibitors are widely used in treatment of metastatic renal cell carcinoma. In paradoxical hematological effect with tyrosine kinase inhibitor therapies, hemoglobin level may be increased, but polycythemia requiring phlebotomy is very rare. Case description We present here a case of renal cell carcinoma who received successive treatment with sunitinib, everolimus, and axitinib. While he had a normal hemoglobin level with prior sunitinib treatment, on the sixth week of axitinib treatment, he developed polycythemia and treatment response was seen after axitinib-associated polycythemia. Conclusion Progression-free survival (PFS) was 30 months in our case with third-line treatment axitinib. Higher hemoglobin levels may be associated with longer survival. Polycythemia was the first response to treatment of axitinib in our patient. It may be an indicator of persistent treatment response.

scholarly journals Predictors of Response to Targeted Therapy in Renal Cell Carcinoma

2012 ◽  
Vol 136 (5) ◽  
pp. 490-495 ◽  
Author(s):  
Laurie J. Eisengart ◽  
Gary R. MacVicar ◽  
Ximing J. Yang
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
High Dose ◽  
Predictors Of Response ◽  
Personalized Approach

Context.—The prognosis for patients with metastatic renal cell carcinoma is poor, with an average 5-year survival of approximately 10%. Use of traditional cytokine therapy, specifically high-dose interleukin 2, is limited by significant toxicity. Better understanding of the molecular pathogenesis of renal cell carcinoma has led to the development of targeted therapies to inhibit specific cellular pathways leading to tumorigenesis. These drugs provide improved survival with a more favorable toxicity profile. There is ongoing investigation of markers that predict response of an individual patient to different targeted therapies. Objective.—To explain the molecular basis for vascular endothelial growth factor inhibitor (antiangiogenic) and mammalian target of rapamycin inhibitor therapies for renal cell carcinoma, summarize the clinical trials demonstrating the effectiveness of these drugs, and describe the biomarkers shown to correlate with outcome in patients treated with targeted therapy. Data Sources.—All included sources are from peer-reviewed journals in PubMed (US National Library of Medicine). Conclusion.—Emerging evidence shows promise that biomarkers will be useful for predicting an individual patient's response to targeted therapy, leading to a more personalized approach to treating renal cell carcinoma.

Treatment Strategies in Metastatic Renal Cell Carcinoma

2010 ◽  
Vol 06 (02) ◽  
pp. 41
Author(s):  
Alain Ravaud ◽  
Jean Christophe Bernhard ◽  
Marine Gross-Goupil ◽  
◽  
◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Treatment Strategies ◽  
Growth Factor Receptor ◽  
Clinical Effects ◽  
Improved Outcomes ◽  
Endothelial Growth Factor

Metastatic renal cell carcinoma (mRCC) is associated with a poor clinical outcome. Until recently, treatment recommendations were limited to immunotherapy and nephrectomy; however, an increased understanding of the molecular biology of RCC has led to the advent of targeted therapies directed against vascular endothelial growth factor/receptor (VEGF/VEGFR) or the mammalian target of rapamycin (mTOR) pathways, both major mediators of tumour growth and progression. These targeted agents have significantly improved outcomes in patients with mRCC, revolutionising treatment. These treatments have overlaps and important distinctions in terms of clinical effects, toxicity and patient populations in which they have been investigated. Concerns in terms of the appropriate sequencing of these agents, their combined use and their role in the context of nephrectomy have emerged as clinically relevant and are being actively investigated.

scholarly journals Hypoxia-Inducible Factor-2 Alpha as a Novel Target in Renal Cell Carcinoma

2021 ◽  
Vol 8 (2) ◽  
pp. 1-7
Author(s):  
WonSeok W. Choi ◽  
Julia Boland ◽  
Jianqing Lin
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Hypoxia Inducible Factor ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau ◽  
Treat Ment ◽  
Promising Therapeutic Target ◽  
Novel Target ◽  
Endothelial Growth Factor

Hypoxia-inducible factor (HIF), an important mediator of hypoxia response, is implicated in tumorigenesis in the setting of pseudohypoxia, such as in the inactivation of von Hippel–Lindau tumor suppressor protein (pVHL), leading to development and progression of clear cell renal cell carcinoma (ccRCC). Targeting downstream molecules in HIF pathway, such as vascular endothelial growth factor (VEGF), has led to improvement in clinical outcome for patients with advanced ccRCC, but such therapy thus far has been limited by eventual resistance and treat-ment failure. Following the discovery of HIF-2 alpha playing a key role in ccRCC carcinogenesis, inhibitors targeting HIF-2 alpha have been developed and have demonstrated encouraging efficacy and safety profile in clinical trials. This review discusses HIF-2 alpha as a promising therapeutic target for ccRCC.

scholarly journals Developing an algorithm for the management of Renal Cell Carcinoma: focus on metastatic disease

2017 ◽  
Vol 8 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Anastasios Kyriazoglou ◽  
Ioannis Dimitriadis ◽  
Aristotelis Bamias
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Incidental Finding ◽  
Mammalian Target Of Rapamycin ◽  
Future Research ◽  
Scientific Papers ◽  
Treatment Paradigm ◽  
Programmed Death 1 ◽  
Endothelial Growth Factor

Abstract The treatment paradigm in renal cell carcinoma (RCC) is rapidly changing. The incidental finding of small renal tumours combined with the development of novel therapeutic agents targeting the vascular endothelial growth factor (VEGF) or the mammalian target of rapamycin (mTOR) pathways or inhibiting the interaction of the programmed death 1 (PD 1) receptor with its ligand have dramatically improved the prognosis of patients suffering from this malignancy. At the same time, the availability of multiple effective options with similar indications complicates the development and applicability of guidelines in this disease. We conducted a systematic review of the existing guidelines. Our study revealed areas of agreement as well as of discrepancies amongst the published scientific papers included. By critically evaluating these areas, we developed a therapeutic algorithm for RCC. We suggest that this methodology can define the practices of wide applicability and areas of future research.

scholarly journals Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function

2021 ◽  
Author(s):  
Łukasz Mielczarek ◽  
Anna Brodziak ◽  
Paweł Sobczuk ◽  
Maciej Kawecki ◽  
Agnieszka Cudnoch-Jędrzejewska ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Kidney Function ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Renal Toxicity ◽  
Checkpoint Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Approved Drugs

AbstractThe introduction of novel targeted therapies during the last 2 decades has led to a significant improvement in patients' clinical outcomes with renal cell carcinoma. However, this improvement came at the price of a whole new spectrum of adverse events, including renal toxicity. Systemic treatment of patients with kidney neoplasms who often present with impairment of kidney function, even prior to treatment, poses an increasing diagnostic and therapeutic challenge for clinicians. Common lifestyle-related comorbidities, i.e., hypertension and diabetes, may contribute to further impairment of kidney function. The lack of official guidelines and the exclusion of patients with reduced kidney function from the clinical trials of recently approved drugs complicate the issue even further. Early detection and correct management of renal toxic effects are crucial to preserve kidney function and ensure the optimal administration of life-prolonging therapies. This review presents detailed information on the renal toxicities of three groups of drugs commonly used in renal cell carcinoma treatment: tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and immune checkpoint inhibitors. We outline the incidence and underlying mechanisms of renal adverse effects with a focus on patients on renal replacement therapy, as well as present suggestions for their management.

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