Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of VEGF (vascular endothelial growth factor) and EGFR (epidermal growth factor receptor) is detected in malignant tumors, and it is associated with poor prognosis. Bevacizumab is a monoclonal anti-body targeting VEGF, and cetuximab and panitumumab are monoclonal anti-bodies targeting EGFR. In some clinical trials, these drugs brings a survival benefit with acceptable toxicity. In Western, bevacizumab, cetuximab and panitumumab have been already approved for patients with unresectable colorectal cancer, and used in clinical practice. In Japan, bevacizumab was approved in April 2007, cetuximab and panitumumab probably will be approved within several years. It is very important to know their efficacy and safety of these drugs for the clinical practice of Japanese patients.
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PMID:[Molecular target therapy and chemotherapy for advanced colorectal cancer]. 1848 7

Molecular-targeted agents, trastuzumab, lapatinib or bevacizumab, demonstrated efficacy in patients with breast cancer. Trastuzumab exhibited efficacy and safety for HER2-positive metastatic breast cancer, in single usage or in combination with paclitaxel, docetaxel or vinorelbine. Trastuzumab is also useful in an adjuvant setting in HER2-positive early breast cancer. However, it is not clear whether concurrent or sequential treatment is superior. Lapatinib combined with capecitabine showed efficacy against HER2-positive metastatic breast cancer. It was suggested that the combination with lapatinib and paclitaxel was effective. Bevacizumab combined with paclitaxel revealed efficacy for metastatic breast cancer. These molecular-targeted agents play an important role in treatment of breast cancer.
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PMID:[Combined chemotherapy with molecular-targeted agent for breast cancer]. 1848 8

In the past few years many encouraging advancements have been made in understanding the molecular mechanisms underlying carcinogenesis and tumor progression. These improvements have led to the identification of promising new targets for cancer therapy. There has been much success with the HER2 targeting antibody trastuzumab (Herceptin) in the treatment of early stage and metastatic breast cancer. Consequently, several antibodies inhibiting cellular signaling of VEGF and EGFR were tested with respect to their efficacy in breast cancer. In phase II and III clinical trials the humanized anti-VEGF antibody bevacizumab (Avastin) alone or in combination with capecitabine exhibited responses in patients with metastatic breast cancer. Recent developments focus on small molecules interfering with different signal transduction pathways in tumor cells. Numerous inhibitors of EGF and VEGF receptor tyrosine kinases and farnesyl transferases are in early stages of clinical development for breast cancer. Another promising approach is the targeting of endothelins and their two G-protein coupled receptors (ET(A)R und ET(B)R). In this article, we will shortly outline well established targeted treatments and discuss the current development of novel agents to be utilized for molecular targeted breast cancer therapy. Due to the heterogeneity of disease and varying response to conventional systemic therapies, these new perceptions may lead to substantial patient benefit and provide a promising basis for future clinical application.
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PMID:Targeted therapies in breast cancer: established drugs and recent developments. 1869 Aug 83

The ability of human tumor cell lines to produce various cytokines, chemokines, angiogenic and growth factors was investigated using Luminex multiplex technology. Media conditioned by tumor cells protected tumor cells from drug-induced apoptosis and stimulated tumor cell proliferation. Antibodies neutralizing IL-6, CXCL8, CCL2 and CCL5 blocked this stimulation. Treatment of tumor cells with doxorubicin and cisplatin resulted in a substantial increase in the production of IL-6, CXCL8, CCL2, CCL5, BFGF, G-CSF and VEGF. This stimulation was associated with drug-induced activation of NF-kappaB, AP-1, AP-2, CREB, HIF-1, STAT-1, STAT-3, STAT-5 and ATF-2 transcription factors and upregulation of IL-6, CXCL8, FGF-2, CSF-3 and CCL5 gene expression. Treatment of tumor cells with doxorubicin and antibodies neutralizing G-CSF, CCL2 or CCL5 had higher inhibitory effects than each modality used alone. These results indicate that chemokines and growth factors produced by tumor by binding to the cognate receptors on tumor and stroma cells could provide proliferative and antiapoptotic signals helping tumor to escape drug-mediated destruction. Clinical studies showed that antibodies neutralizing VEGF (Avastin/Bevacizumab) or blocking HER2/neu signaling (Herceptin/Trastuzumab) could increase the efficacy of chemotherapy, although these beneficial effects have been limited. It is possible that drug-stimulated production of growth and proangiogenic factors could counterbalance the effects of antibody therapy. In addition, numerous growth factors and chemokines share angiogenic and growth-stimulating properties, and thus reduction of a single factor is insufficient to completely block tumor growth. Thus, a broad disruption of tumor cytokine network is needed to further increase the efficacy of cancer therapy.
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PMID:Chemotherapeutic drugs and human tumor cells cytokine network. 1869 97

Breast cancer is the most common malignancy in women worldwide, and represents the leading cause of death in the female population. Incidence of breast cancer increases with age, and older patients are more likely to have disseminated disease at diagnosis. For those patients who relapse after endocrine treatment or in which the tumor does not express hormone receptors, chemotherapy should be considered. Single agent sequential regimens should be preferred to combination regimens, which are usually more toxic and provide a limited survival gain. New drugs which have proven efficacy against metastatic breast cancer are Taxanes (Paclitaxel and Docetaxel), Vinorelbine, Capecitabine, Gemcitabine, various and newer formulations of Anthracyclines (Epirubicin, oral Idarubicin, liposomal Doxorubicin). The anti-HER2 monoclonal antibody Trastuzumab in association with chemotherapy can be administered to elderly patients who present with HER2 overexpressing tumors, though cardiac monitoring is necessary due to cardiac adverse events. Bevacizumab, an anti-VEGF monoclonal antibody, was recently patented and approved in combination with Paclitaxel for the treatment of metastatic breast cancer. Globally, there is need to develop therapeutics able to circumvent resistance against hormonal and other therapies for advanced breast cancer, which are expected to be safe and effective in this age class.
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PMID:Chemotherapy and targeted agents for elderly women with advanced breast cancer. 1899 87

Angiogenesis is tightly regulated by opposing mechanisms in mammalian cells and is controlled by the angiogenic switch. Other review articles have described a central role for the PTEN/PI-3 kinase/AKT signaling node in the coordinate control of cell division, tumor growth, apoptosis, invasion and cellular metabolism [1, 2]. In this review, we focus on literature that supports the PTEN/PI-3 kinase/AKT signaling node as a major control point for the angiogenic switch in both the on and off positions. We also discuss the rationale for designing small molecule drugs that target the PTEN/PI-3 kinase/AKT signaling node for therapeutic intervention. Our hypothesis is that, instead of inhibiting one cell surface receptor, such as VEGFR2 with bevacizumab (Avastin), thereby leaving a significant number of receptors free to pulse angiogenic signals, a more effective strategy may be to regulate signaling through an intercept node where redundant cell surface receptor signals converge to transmit important signaling events within the cell. This therapeutic configuration brings coordinate control over multiple cell surface receptors in concert with a physiologic response which may combine arrest of cell cycle progression with growth inhibition and the induction of genes involved in specialized functions such as movement, which are all required for the complex process of angiogenesis to occur in a temporal-spatial paradigm.
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PMID:PI-3 kinase-PTEN signaling node: an intercept point for the control of angiogenesis. 1919 65

Neoplastic angiogenesis is an essential process in the progressive growth of neoplasms and the production of metastasis. Angiogenesis consists of a series of linked and sequential steps that ultimately leads to the development of a neovascular blood supply to the tumor mass. VEGF has got an essential role in neoplastic angiogenesis, therefore it is an important target in the treatment of neoplasms. Bevacizumab, a humanized monoclonal antibody, inhibits VEGF, and may also improve the delivery of chemotherapy to the tumor mass. Multi-kinase ihibitors (sorafenib and sunitinib) are orally administered small-molecules, that inhibit different receptors (essentials in the neoplastic angiogenesis), such as the VEGFR or PDGFR. These agents are useful in the treatment of advanced renal-cell carcinoma, and are under investigation in several tumors.
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PMID:[Neoplastic angiogenesis]. 1929

Increased levels of vascular endothelial growth factor (VEGF) have been associated with a poor prognosis for patients with breast cancer. In addition to its prognostic role, VEGF is also a validated target in the treatment of this disease. Bevacizumab, an anti-VEGF antibody, has demonstrated significant clinical benefit in several solid tumors, including breast cancer. Its use in combination with either paclitaxel or docetaxel has prolonged progression-free survival and increased response rates in the first-line treatment of patients with metastatic, HER2-negative breast cancer. In this paper, the clinical trials establishing bevacizumab use for the treatment of breast cancer are reviewed.
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PMID:Bevacizumab in the treatment of metastatic breast cancer. 1947 63

The selection of first-line chemotherapy for metastatic breast cancer (MBC) is complex because of the myriad of treatment options available and the inherent biologic heterogeneity of the disease. The potential treatment options are greatly influenced by estrogen and progesterone receptor and HER2 status of the tumor, and biopsy with reassessment of these markers at the time of disease recurrence is strongly recommended. Metastatic breast cancer is generally an incurable disease, with survival that could range from months to several years. Important but modest improvements in overall survival (OS) have been observed for women with MBC over the past few decades, in part because of improvements in systemic therapy. For women with endocrine-responsive disease, hormonal therapy is the appropriate initial treatment choice at the time of disease recurrence with rare exception. Initiation of systemic chemotherapy is appropriate for women with disease that is either hormone receptor negative, endocrine therapy refractory, or rapidly progressive with visceral involvement. The addition of trastuzumab to chemotherapy for women with HER2-positive breast cancer represents a clear standard of care. For HER2-negative MBC, sequential single-agent chemotherapy is preferred over combination therapy as a result of the more favorable toxicity profile and absence of a clinically significant improvement in survival with combination treatment. Many single-agent chemotherapeutic agents have activity in MBC, with most data supporting an anthracycline- or taxane-based approach. Bevacizumab in combination with chemotherapy prolongs progression-free survival in women with MBC, though its position in the first-line treatment of MBC relative to standard chemotherapy remains unclear at this time because of lack of OS benefit.
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PMID:First-line chemotherapy for metastatic breast cancer. 1959 45

The colorectal cancer treatment has significantly changed in last few years. Use of new drugs such as oxaliplatin, irinotecan, or capecitabine improved long term survival of patient with this disease. Research of biologic and genetic behavior of CRC has brought new ways in therapy called "biologic therapy". Standard today's treatment consist of three drugs: bevacizumab (antiVEGF antibody), cetuximab and panitumimab (anti EGFR antibodies). Biology therapy should be used simultaneously with chemotherapy only and after genetic examination of the cancer (K ras mutation). For patients with stage III the adjuvant therapy with combination of FOLFOX (oxaliplatin, fluorouracil, and leukovorin) is recommended to reduce the probability of recurrence and improve survival. In stage IIB there is a clear need to determine further risks which classify the high risk patients who should be enrolled in adjuvant chemotherapy. In palliative treatment of colorectal cancer there are several chemotherapy combinations (FUFA, FOLFOX, FOLFIRI, XELOX, XELIRI) used with biologic therapy. International recommendation for the biologic therapy is in the first line treatment bevacizumab and cetuximab or panitumumab in the second line is recommended. The new discoveries in biology of colorectal cancer show the need of tailoring.
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PMID:[Chemotherapy and biological treatment in the complex management of large intestinal and rectal carcinomas. When, why, how?]. 1964 20


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