Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bladder cancer is an urologic common tumor after prostatic carcinoma. Treatment of bladder cancer requires an interdisdisciplinary approach, including urologist, medical oncologist and radiation oncologist. Treatment of superficial tumors is based on endovesical instillations and sometimes on radical cystectomy for pejorative recurrences. For invasive tumor, radical cystectomy is needed. At present, ileal reconstructions could be largely proposed, in men as in women, for better quality of life. For selected patients, chemoradiotherapy is a valid alternative treatment to radical cystectomy, with similar survival rates and conservation rates of functional bladder about 50-60 %. In spite of the efficacy of local treatment, almost one half of patients develop metastasis. Recently, new drugs like paclitaxel, gemcitabine or Herceptin are available to improve the management of metastatic disease.
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PMID:[Bladder cancer: realities and perspectives]. 1260 6

The HER-2/neu gene is frequently amplified in bladder cancer. Topoisomerase 2 Alpha (TOP2A) which is located nearby the HER-2/neu gene is an important molecular target for several anti cancer drugs. The frequency of TOP2A amplification in urinary bladder cancer is unknown. It was the aim of this study to determine the frequency of HER-2 and TOP2A amplification in urinary bladder cancer and to evaluate the association of these amplifications with tumor phenotype. For this purpose a tissue microarray containing 768 pTa, 425 pT1 and 571 pT2-4 carcinomas was analyzed by fluorescence in situ hybridization (FISH). Amplifications of both genes were significantly associated with advanced tumor stage and high grade. HER-2 amplification was found in 1.6% of pTa, 7.2% of pT1 and 13.8% of pT2-4 carcinomas (p < 0.0001). HER-2 amplification was present in only 1.1% of grade 1 and 0.8% of grade 2 tumors but in 14.2% of grade 3 tumors (p < 0.0001). TOP2A amplification was present in 0.7% pTa, 1.8% pT1 and 3.4% pT2-4 carcinomas (p < 0.0001). TOP2A was found in none of the grade 1, in 0.2% of grade 2 and 3.8% of grade 3 tumors (p < 0.0001). 1% of all analyzed tumors had simultaneously high level amplification of TOP2A and HER-2. Amplification of both genes were significantly associated with tumor specific survival if all tumors were analyzed together. Given the high frequency of HER-2 amplification in urinary bladder cancer, some of these tumors may respond favorable to Herceptin therapy. The TOP2A amplification status may influence response to anthracyclin treatment.
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PMID:[HER-2 and TOP 2A gene amplifications in urinary bladder carcinoma]. 1264 67

The Cancer and Leukemia Group B (CALGB) Genitourinary Committee has developed a broad range of clinical trials across most stages of bladder cancer. Recurrence rates of superficial bladder cancer after transurethral resection range from 50-70%. Although adjuvant bacillus Calmette-Guerin reduces the risk of disease recurrence or progression, only 30% of patients have long-term disease-free survival. Because the development of novel secondline agents is needed, the CALGB is evaluating the utility of intravesicle gemcitabine as well as an oral proapoptotic agent (CP-461). In patients with locally advanced disease with an increased risk of disease recurrence after cystectomy, a randomized trial of conventional chemotherapy versus sequential dose-dense therapy is under development. The gemcitabine/cisplatin combination has become a commonly used regimen for the treatment of advanced transitional cell carcinoma (TCC). The CALGB is undertaking a Phase II study that incorporates a fixed dose rate gemcitabine infusion in this regimen, together with a selective epidermal growth factor receptor tyrosine kinase inhibitor, Iressa (Astra Zeneca, Wilmington, DE). In patients with renal insufficiency, a regimen of carboplatin, gemcitabine, and Iressa is planned. Novel agents, including arsenic trioxide and trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), are being evaluated as secondline therapy in patients with advanced TCC who have disease progression after frontline therapy.
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PMID:Overview of bladder cancer trials in the Cancer and Leukemia Group B. 1267 1

The improved understanding of the molecular biology of urothelial malignancies is helping to define the role of new targets and prognostic indices that can direct the most appropriate choice of treatment for advanced disease. Many human tumors express high levels of growth factors and their receptors that can be used as potential therapeutical targets. Tyrosine-kinase receptors, including many growth factor receptors such the receptors for epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and Her2/neu, have been found overexpressed in urothelial tumors. For many of these growth factor receptors, the degree of expression has been associated with the progression of cancer and a poor prognosis. Among the best studied growth factor receptors are the two members of EGF receptor familiy EGFr (ErbB-1), and Her2/neu (ErbB-2). Several preclinical studies in bladder cancer models, have confirmed that systemic administration of growth factor inhibitors inhibits the growth and metastasis of human transitional cell carcinoma established in the bladder wall of athymic nude mice. Additional studies indicate that therapy with EGFR inhibitors enhances the activity of conventional cytoreductive chemotherapeutic agents, in part by inhibiting tumor cell proliferation, angiogenesis, and inducing apoptosis. Novel targeted therapy hold promise to improve the current results of bladder cancer treatment. Based on the success seen with anti-HER2 monoclonal antibodies (Herceptin) and the promising results with EGFR targeted agents (IMC-C225 Cetuximab, ZD1389 Iressa, OSI-774 Tarceva, GW 57016) in other tumor types, and based on the results obtained in preclinical models, there is a great interest in assessing these agents in patients with bladder cancer. Several trials are now ongoing testing these new agents alone or in combination with chemotherapy in bladder cancer patients. The integration of these newer biologic agents, probably to supplement rather than to supplant chemotherapeutic drugs, should be a primary direction of research with the objective to interfere with multiple aspects of bladder cancer progression. However, the value of integration of biologically targeted agents into combined modality treatment for patients with bladder cancer has still to be proven.
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PMID:Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family. 1285 May 30