Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.
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PMID:Evolving role of novel targeted agents in renal cell carcinoma. 1792 97

The management of advanced renal cell carcinoma (RCC) is undergoing a revolution, with the introduction of new agents and surgical paradigms. Thoughtful integration of diagnostic, surgical and medical approaches to the patient is paramount for disease control. Methods of risk stratifying kidney cancers are reviewed, as well as mechanisms of action of newer drugs approved in advanced metastatic kidney cancer. These drugs present opportunities for application to patients in an earlier stage of disease, and adjuvant RCC trials designs are discussed. Improvements have been made in the understanding of the molecular and genetic basis of RCC, both for causative and prognostic markers, with models addressing prediction of tumor behavior and therapeutic targets. Practice patterns have shifted from cytokine therapies to targeted molecular approaches, particularly emphasizing the VEGF pathway, related intracellular kinases and the mammalian target of rapamycin. Autologous vaccine adjuvant studies are maturing. In conclusion, elucidation of specific genes, proteins and aberrant molecular pathways associated with kidney cancer are ongoing. These new agents may lead to opportunities to improvement of disease-free survival through therapy in the adjuvant setting.
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PMID:Growing opportunities for adjuvant therapy of renal cell carcinoma: targeted drugs and vaccines. 1800 Dec 57

Until 2006, immunotherapy (interferon-alpha or interleukin 2) was the standard medical treatment for metastatic renal cell carcinoma (RCC), and its results were disappointing: despite a few cases of complete response with prolonged survival, median survival was one year. Better understanding of the molecular mechanisms of tumor angiogenesis, especially in clear cell carcinoma, has led to the development of multiple targeted therapies to inhibit key effectors: vascular endothelial growth factor (VEGF), VEGF receptor, and mTOR (target of rapamycin). Two inhibitors targeting several protein kinases, including the VEGF receptor, have increased progression-free survival in patients with metastatic RCC and are now commercially available: sunitinib (Sutent) as first-line treatment and sorafenib (Nexavar) as second-line treatment. These targeted therapies will certainly affect overall survival, but it is too early for any firm conclusions. Their side-effects, usually low or moderate, include asthenia, anorexia, diarrhea, hand-and-foot syndrome and hypertension. Optimal management is required to ensure prolonged exposure. Other drugs have been effective: bevacizumab (Avastin), a monoclonal antibody inhibiting VEGF, increases progression-free survival as second-line treatment, and temsirolimus (Torisel), an mTOR protein kinase inhibitor, increases overall survival in the population of patients with poor prognosis. These targeted drugs will serve as the basis for development of future therapeutic strategies.
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PMID:[Renal cell carcinoma and antiangiogenic therapies]. 1803 17

Systemic therapy of metastatic kidney cancer has undergone dramatic changes over the past years. One reason for this is our increasing knowledge of different histological subtypes and associated genetic aberrations. Furthermore, signalling pathways have been identified to be relevant for tumour progression and therapeutic intervention. Until some years ago, systemic therapy for kidney cancer consisted of cytokines. In this review, new drugs for the treatment of metastatic kidney cancer are discussed. These drugs predominantly interact the VEGF, EGFR and mTOR signalling pathways. Four drugs have been studied in phase III trials and were (or will soon be) approved for treatment of metastatic kidney cancer. Additionally, many drugs are currently being tested in phase I and phase II trials. At present, the following scenarios have an impact on therapy decisions: different prognostic groups, first-line and second-line therapy, combination therapies and the impact of different histological subtypes.
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PMID:[New drugs for metastatic kidney cancer]. 1830 3

In this review, pathogenesis and genetic alterations of urologic malignancies and their therapeutic target molecule are summarized briefly. In bladder cancer, only a little has been revealed. Loss of heterozygosity of 9p/q is frequently observed in low grade, low stage tumors. In invasive or carcinoma in situ tumors, alteration of p53 and Rb tumor suppressor gene is frequently found. In prostate cancer, the process of carcinogenesis from normal epithelium to cancer hypothesized by Nelson et al. (N Engl J Med 24; 349 : 366-381) seems to be logic. Androgen independency of tumor cells is associated with androgen receptor gene mutation and amplification, however, the mechanism is not well clarified. It is a turning point, therapeutic strategy is changing from cytokine immunotherapy to molecular targeting therapy in metastatic renal cell carcinoma. The pathway from growth factors such as vascular endothelial growth factor and platelet derived growth factor, and their receptors to mTOR is a central controller of tumor angiogenesis and proliferation.
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PMID:[Tumor inhibitory factors in urologic malignancies]. 1826 Mar 61

Treatment of patients with metastatic renal cell carcinoma is evolving rapidly due to the advent of novel targeted therapies. Improved knowledge of the underlying pathogenesis has led to the development of drugs that modulate the dominant signal transduction pathways for this disease, which results in inhibition of angiogenesis. Recent evidence indicates that the receptor tyrosine kinase inhibitor sunitinib prolongs progression-free survival compared with interferon-alpha, especially in patients with intermediate risk. Immunotherapy with interferon-alpha or high-dose interleukin-2 should still be considered for low-risk patients, particularly those with clear-cell tumours and metastases of the lung only. In patients who fail treatment with interferon-alpha, sorafenib has been shown to improve progression-free survival. High-risk patients may benefit from treatment with temsirolimus, which inhibits mammalian target of rapamycin (mTOR) kinase activity and has shown to improve overall survival. These angiogenesis inhibitors did not receive mention in the recently published guideline 'Renal cell carcinoma'.
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PMID:[Angiogenesis inhibitors for the systemic treatment of metastatic renal cell carcinoma: sunitinib, sorafenib, bevacizumab and temsirolimus]. 1838 Mar 84

Metastatic renal cell carcinoma (RCC) has a poor overall survival. Localized RCC remains a surgical disease. About 20%-30% patients who present with limited disease at the time of nephrectomy develop metastasis. The median time to relapse after nephrectomy is 15-18 months. The maximum numbers of relapses are within the first 3 years. In metastatic RCC, immunotherapy is effective in a relatively small percentage of patients but is very toxic. In recent years, there has been an improved understanding of the biology of RCC. This has lead to the development of various agents that target ligands at the molecular level. The hypoxia inducible factor-alfa (HIF-)/ vascular endothelial growth factor (VEGF) pathway and mammalian target of rapamycin (mTOR) signal transduction pathway are targets for some of these novel agents. Recent randomized phase III trials have shown an improved outcome in patients with metastatic disease who received these targeted agents. This review deals with management of advanced and metastatic renal cell cancer with an emphasis on recently developed targeted therapies.
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PMID:Treatment options for metastatic renal cell carcinoma: a review. 1840 42

For many years immuno(chemo)therapy has been the only therapeutic option for patients with metastatic renal cell carcinoma. Few patients, however, experienced long-term disease control and toxicity was considerable. Recent advances in understanding the biology and genetics of this malignancy have led to novel-targeted therapeutic approaches. Since 2003, a multitude of new drugs have been developed and tested, with small molecule tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors and monoclonal antibodies appearing to be the most promising agents. In the following, we give a concise overview on results of current trials in metastatic renal cell carcinoma published within 2007. Moreover, we will translate these results into therapeutic options and recommendations.
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PMID:Metastatic renal cell carcinoma: recent advances and current therapeutic options. 1851 Jan 69

Therapeutic approaches based solely on cytokine are meanwhile no longer recommended without restrictions as the primary therapy for metastatic renal cancer due to the reduced clinical response and the promising available data regarding molecular therapy. Several randomized controlled studies have been performed since the introduction of the so-called targeted therapies for metastatic renal cancer. Substantial data relevant for drug approval are available for the multikinase inhibitors sorafenib (Nexavar) and sunitinib (Sutent), the mTOR inhibitor temsirolimus (Torisel), and the monoclonal antibody bevacizumab (Avastin) in combination with interferon-alpha. Sunitinib, temsirolimus, and bevacizumab are approved for first-line treatment, whereas sorafenib was approved for second-line treatment in Germany.Clinical trials are currently investigating the questions of optimal timing, value of neoadjuvant or adjuvant treatment, form, and sequence of the molecular targeted therapy. Experimental investigations for a better understanding of signaling pathways will preferably allow preselecting patients for an individualized therapy in metastatic renal cell cancer (RCC). The aim of the present paper is to address and to critically discuss the clinical data that are currently available regarding"targeted" therapeutics during the treatment of metastatic RCC.
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PMID:[Value of targeted therapies for renal cell cancer]. 1858 56

The effectiveness of multikinase inhibitors in first- and second-line therapy of metastatic renal cell carcinoma (RCC) has been evaluated in various clinical studies. Initial results indicate an increased response rate and a prolonged progression-free survival compared with cytokine-containing therapeutic approaches. The new multitargeted kinase inhibitors sorafenib (Nexavar/BAY 43-9006) and sunitinib (Sutent/SUO 11248) interfere mainly with vascular endothelial growth factor and platelet-derived growth factor pathways. Recently, temsirolimus, a specific inhibitor of mammalian target of rapamycin, demonstrated activity in RCC patients with poor prognosis. This review discusses the effectiveness of the most frequently used substances for systemically progressive RCC in consideration of the currently available clinical data.
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PMID:An update on the medical therapy of advanced metastatic renal cell carcinoma. 1861 63


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