Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Westernised countries, colorectal cancer (CRC) is second only to lung cancer as a cause of death from malignancy, with only 60% of patients alive at 5 years. In Stage II/III CRC, where the standard treatment is 5-fluorouracil (5-FU)/leucovorin, a recent clinical trial has shown that with the addition of oxaliplatin, fewer patients have relapsed or died at 40 months follow-up. The benefit was more pronounced in patients with Stage III than II CRC, and the addition of oxaliplatin to 5-FU/leucovorin should be considered in Stage III CRC. In metastatic CRC, where the standard treatment is 5-FU/leucovorin/irinotecan, a recent clinical trial has shown that the addition of bevacizumab, a mAb, to vascular endothelial growth factor, prolonged progression-free and overall survival. Bevacizumab is likely to become part of the standard therapy for metastatic CRC.
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PMID:Which drug combination for colorectal cancer? 1557 79

Angiogenesis is characterized by the development of new vasculature from pre-existing vessels and plays a central role in physiological processes such as embryogenesis, wound healing and female reproductive function, as well as pathophysiologic events including cancer, rheumatoid arthritis and diabetic retinopathy. The growth and metastasis of tumors is critically dependent upon angiogenesis. Although targeting angiogenesis as a therapeutic strategy has to date met with limited success in the clinic, the recent FDA approval of the anti-VEGF antibody Avastin has validated the use of anti-angiogenic therapeutic strategies for cancer treatment. We have recently identified several plasma proteins having anti-angiogenic properties, including Histidine-Proline-Rich Glycoprotein (HPRG) and activated high-molecular-weight kininogen (HKa). Both of these proteins are able to induce apoptosis in endothelial cells in vitro and can inhibit angiogenesis in vivo. Recent studies from our laboratories have also identified a novel cell-surface binding protein for HKa that mediates its anti-angiogenic activity. This protein, tropomyosin, is normally found inside the cell and is associated with the actin cytoskeleton, where it plays a critical role in stabilizing actin filaments in a variety of cell types. However, in angiogenic endothelial cells, tropomyosin appears to have extracellular localization. Previous studies have also suggested the involvement of tropomyosin in the anti-angiogenic activity of endostatin, and our recent work indicates that tropomyosin may mediate the antiangiogenic activity of HPRG as well. In this review, we summarize data describing extracellular tropomyosin as a novel receptor for multiple anti-angiogenic proteins. Extracellular tropomyosin may therefore represent a previously undescribed central target for the development of anti-angiogenic therapy.
Curr Cancer Drug Targets 2004 Nov
PMID:Extracellular tropomyosin: a novel common pathway target for anti-angiogenic therapy. 1557 12

A search of the Medline database and ASCO 2003 conference proceedings was conducted to identify clinical trials currently underway using single-agent therapy for renal cell carcinoma (RCC). Combination trials were identified using the ASCO 2003 conference proceedings. Fourteen single-agent therapies employing different mechanisms of action were identified in the published literature: imatinib mesylate (Gleevec); bevacizumab (Avastin); thalidomide (Thalomid); gefitinib (ZD1839) (Iressa); cetuximab (IMC-C225) (Erbitux); bortezomib (PS-341) (Velcade); HSPPC-96 (Oncophage); BAY 59-8862; ABT-510; G250; CCI-779; SU5416; PTK/ZK; and ABX-EGF. Six distinct fields of clinical research have emerged: monoclonal antibodies, small molecules, vaccines, second-generation taxanes, nonapeptides and immunomodulators. Five combination regimens, primarily biological response modifiers (interleukin-2 or interferon-alpha), chemotherapy- or thalidomide-based, were identified. All therapies demonstrated acceptable toxicity profiles. Clinical benefit was assessed based on each study's reported criteria: antitumor response (regression or stability) ranged from 5% to 71%. In the past several years, significant advances in the underlying biological mechanisms of RCC, particularly the role of tumor angiogenesis, have permitted the design of molecularly targeted therapeutics. Based on preliminary and limited studies, combination therapies offer the greatest clinical benefit in the management of this malignancy, although additional basic research is still warranted.
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PMID:Renal cell carcinoma: review of novel single-agent therapeutics and combination regimens. 1559 29

Tumor growth and metastasis are angiogenesis-dependent. Anti-angiogenic therapy represents a new strategy for the development of anti-cancer therapies. In recent years, there has been made great progress in anti-angiogenic therapy. As far as the passive immunotherapy is concerned, a recombinant humanized antibody to vascular endothelial growth factor (VEGF)--Avastin has been approved by FDA as the first angiogenesis inhibitor to treat colorectal cancer. For active specific immunotherapy, various strategies for cancer vaccines, including whole endothelial cell vaccines, dendritic cell vaccines, DNA vaccines, and peptides or protein vaccines, have been developed to break immune tolerance against important molecules associated with tumor angiogenesis and induce angiogenesis-specific immune responses. This article reviews the angiogenesis-targeted immunotherapy of tumor from the above two aspects.
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PMID:Immunotherapy of tumor by targeting angiogenesis. 1562 Jan 11

There is an increasing evidence of the crucial role of angiogenesis in cancer, and randomized studies have indicated that a "pure" anti-angiogenic drug (the anti-VEGF antibody Avastin) is very effective in colorectal cancer. In addition, this and other anti-angiogenic drugs have demonstrated activity and are currently under clinical investigation in a variety of other cancer types. At the present time, however, there is a scarcity of useful endpoints for treatment outcome beside survival. Using flow cytometry, quantitative PCR and cell culture we have found that circulating endothelial cells and progenitors are increased in cancer patients, and that measuring their viability and kinetics may offer significant clinical insight in the management of cancer patients.
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PMID:Strategies to investigate circulating endothelial cells in cancer. 1569 68

Angiogenesis is critical for normal and pathologic processes in new blood vessel formation. A recent significant advance in the treatment of metastatic colorectal cancer has occurred by the development of agents targeting key regulatory molecules involved in this process, specifically vascular endothelial growth factor (VEGF). These angiogenesis inhibitors, include bevacizumab (Avastin, Genentech, Inc, South San Francisco, CA), which binds free VEGF. Recently, a phase III, multicenter, double-blind, randomized, placebo-controlled trial was designed to determine whether or not the addition of bevacizumab to first-line irinotecan, 5-fluorouracil, and leucovorin chemotherapy was completed in patients with metastatic colorectal cancer. The trial showed a higher response rate, longer time to tumor progression, and prolonged overall survival in patients with metastatic colorectal cancer. Of note, this was the first large, randomized, phase III study to show the importance of targeting VEGF and tumor angiogenesis for the treatment of human cancer. Other potential targets of angiogenesis, such as the VEGF receptor and multi-targeted agents, are undergoing evaluation in clinical trials.
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PMID:Angiogenesis inhibitors in the treatment of colorectal cancer. 1569 25

Pathologic angiogenesis induced by a tumor is essential for its survival. The promise of tumor inhibition by targeting angiogenesis over the past several years has translated into numerous ongoing clinical trials. Recently, in a phase III trial involving patients with metastatic colorectal cancer, Bevacizumab (Genentech, Inc, San Francisco, CA), a recombinant humanized monoclonal antibody against vascular endothelial growth factor used in conjunction with standard chemotherapy was shown to increase survival, progression-free survival, response rate, and duration of response compared to chemotherapy alone. Thus far, duration of the increased response remains less than 6 months. The majority of deaths in patients with colorectal cancer are related to hepatic metastases. It is hoped that novel approaches directed at the complex interactions between tumor and microenvironment in the angiogenic process will strengthen the therapeutic armamentarium against hepatic malignancies.
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PMID:Hepatic tumor growth: target for angiogenesis inhibition? 1570 41

Within the revolution of molecular biology in cancer, it should be pointed out the role of monoclonal antibodies clinically utilized as if they were "magic bullets". From the works of Kohler and Milstein in 1975 the evolution has been fast and its inclusion in daily clinical practice gradual. Among the more significant there is anti-CD20 that has revolutionized the treatment of lymphomas. Currently, antibodies conjugated with isotopes derived from anti-CD20 have been produced. Trastuzumab antibody against HER2/neu has opened new prospects in the treatment of breast cancer. Cetuximab antibody against EGFR has achieved good results in the treatment of chemotherapy-resistent colon cancer. Bevacizumab is perhaps the most promising antibody against solid tumors, having shown effectiveness as first line therapy in metastatic colon cancer in combination with chemotherapy.
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PMID:[Antibodies against cancer]. 1571 74

Angiogenesis, the process of new blood vessel formation, is an essential step in tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is a key mediator in this process, and elevated levels of this cytokine are observed in solid tumors and are correlated with worse clinical outcomes. Research has therefore focused on developing agents that target angiogenic factors such as VEGF in order to inhibit tumor growth. One such agent is bevacizumab, a humanized monoclonal antibody generated by engineering the VEGF-binding residues of a murine neutralizing antibody into the framework of a normal human immunoglobulin G. Bevacizumab recognizes VEGF receptors 1 and 2 and thus can neutralize the biologically active forms of VEGF that interact with these receptors. In addition, bevacizumab has shown antiangiogenic and antitumor activity in several cancer types, recently gaining approval from the FDA for use in combination with fluorouracil-based chemotherapy as a first-line treatment for metastatic cancer of the colon or rectum.
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PMID:Bevacizumab: antiangiogenic cancer therapy. 1575 67

Despite advances in understanding and treatment, ovarian cancer remains a major cause of cancer mortality worldwide. Debulking surgery and paclitaxel/carboplatin chemotherapy induce good initial responses in most patients, although most cases of advanced disease are not controlled. Monoclonal antibodies hold promise as a potential incremental advance for the treatment of the disease. Antibodies can be used to stimulate the immune response, target tumor-specific receptors to induce antibody-dependent cellular cytotoxicity or interfere with biologic pathways. They can also be used to deliver therapeutic radioisotopes to malignant cells. Oregovomab is in Phase III clinical trials as a consolidation treatment post front-line therapy to trigger tumor-specific cellular immunity. Bevacizumab, which blocks vascular endothelial growth factor, will be entering Phase III as an adjuvant to front-line chemotherapy with a direct effect on angiogenesis. Additional immunostimulating, immune counter-regulatory and receptor-targeting approaches are also reviewed. The family of epidermal growth factor receptors including epidermal growth factor receptor 1 (HER-1) and 2 (HER-2) are both expressed in ovarian cancer and are the subject of ongoing research and development. The recent disappointing results with 90-yttrium-labeled anti-HMFG by single intraperitoneal administration have left the radiopharmaceutical field without a Phase III candidate. Identification of novel targets may advance this therapeutic area in the future. The rapid advances in the fields of immunoregulation and tumor biology should permit an accelerated introduction of antibodies for the treatment of ovarian cancer. These antibodies could complement novel small molecules that are also in development.
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PMID:Monoclonal antibody therapy of ovarian cancer. 1575 41


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