554 research outputs found

    The role of bevacizumab in breast cancer

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    AbstractNeoangiogenesis and expression of the main angiogenic factor Vascular endothelial growth factor (VEGF) are critical steps already present at an early stage of breast cancer development. As tumor growth progresses other pro-angiogenic factors, including bFGF, TGFa and IL-8, are overexpressed and act in addition to VEGF. VEGF expression has been associated to poor prognosis and therapy outcome in breast cancer. Moreover, several studies have documented that HER-2 overexpression induces VEGF expression/secretion and neovascularization and that VEGF expression increases when tumors become resistant to treatment. On these bases the anti-VEGF drug Bevacizumab has been evaluated in the clinical setting in breast cancer patients. Recently, phase III studies have demonstrated that Bevacizumab in combination with taxanes produces a high rate of responses and increases the Progression Free survival of breast cancer patients. A large array of studies is currently ongoing with Bevacizumab in combination with chemotherapy and hormone-therapy in the metastatic, neoadjuvant and adjuvant setting

    Panitumumab: the evidence of its therapeutic potential in metastatic colorectal cancer care

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    Colorectal cancer is the fourth most common malignant disease. Of newly diagnosed patients, 40% have metastatic disease at diagnosis, and approximately 25% of patients with localized disease at diagnosis will ultimately develop metastatic disease. The benefits of systemic chemotherapy in the treatment of metastatic colorectal cancer over best supportive care have been established. Panitumumab (ABX-EGF) is the first fully human monoclonal antibody developed for use in colorectal cancer that targets the extracellular domains of epidermal growth factor receptor

    The role of EGFR inhibitors in nonsmall cell lung cancer

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    The epidermal growth factor receptor is a cell membrane receptor that plays a key role in cancer development and progression. Ligand-activated epidermal growth factor receptor-dependent signaling is involved in cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. Targeting the epidermal growth factor receptor represents a promising molecular approach in cancer treatment. Several antiepidermal growth factor receptor agents are in clinical development. This review focuses on the available clinical data on epidermal growth factor receptor-targeting drugs in the treatment of nonsmall cell lung cancer

    Overcoming resistance to molecularly targeted anticancer therapies: rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies

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    Accumulating evidence suggests that cancer can be envisioned as a "signaling disease", in which alterations in the cellular genome affect the expression and/or function of oncogenes and tumour suppressor genes. This ultimately disrupts the physiologic transmission of biochemical signals that normally regulate cell growth, differentiation and programmed cell death (apoptosis). From a clinical standpoint, signal transduction inhibition as a therapeutic strategy for human malignancies has recently achieved remarkable success. However, as additional drugs move forward into the clinical arena, intrinsic and acquired resistance to "targeted" agents becomes an issue for their clinical utility. One way to overcome resistance to targeted agents is to identify genetic and epigenetic aberrations underlying sensitivity/resistance, thus enabling the selection of patients that will most likely benefit from a specific therapy. Since resistance often ensues as a result of the concomitant activation of multiple, often overlapping, signaling pathways, another possibility is to interfere with multiple, cross-talking pathways involved in growth and survival control in a rational, mechanism-based, fashion. These concepts may be usefully applied, among others, to agents that target two major signal transduction pathways: the one initiated by epidermal growth factor receptor (EGFR) signaling and the one converging on mitogen-activated protein kinase (MAPK) activation. Here we review the molecular mechanisms of sensitivity/resistance to EGFR inhibitors, as well as the rationale for combining them with other targeted agents, in an attempt to overcome resistance. In the second part of the paper, we review MAPK-targeted agents, focusing on their therapeutic potential in hematologic malignancies, and examine the prospects for combinations of MAPK inhibitors with cytotoxic agents or other signal transduction-targeted agents to obtain synergistic anti-tumour effects. Originally published Drug Resistance Updates, Vol. 10, No. 3, June 200
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