Expert review of anticancer therapy
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Expert Rev Anticancer Ther · Dec 2007
ReviewCardiotoxicity associated with the use of trastuzumab in breast cancer patients.
The monoclonal antibody against HER2, trastuzumab (Herceptin), has become an important player in the treatment of patients with HER2-positive breast cancer. Both in the metastatic and adjuvant setting, the addition of trastuzumab to other systemic treatments has led to a striking increase in tumor response and survival. The downside with the use of this agent, however, is its inherent cardiotoxicity, which is particularly common when anthracyclines are used concurrently. This review will focus on all aspects of the cardiac side-effects of trastuzumab, ranging from epidemiology and pathophysiology to cardiac monitoring, and treatment and prevention.
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Expert Rev Anticancer Ther · Dec 2007
ReviewSpectrum of pediatric gliomas: implications for the development of future therapies.
The therapy of gliomas is still challenging. This is especially true for pediatric gliomas because response to conventional cytotoxic chemotherapy agents and radiation therapy is currently often poor and because therapy-related morbidity is a significant problem in children. ⋯ These new insights into the molecular mechanism driving tumor growth uncover new potential molecular targets for future therapies. In addition, they start to uncover biologically defined tumor subtypes that may have to be considered independently in the search for optimal treatment regimens.
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Radiotherapy plays a central role in the treatment of pediatric brain tumors. Historically, surgical resection alone was the mainstay of treatment for pediatric CNS malignancies. ⋯ Unfortunately, the long-term CNS side effects of radiotherapy remain a major obstacle for survivors of childhood tumors. In this article we will discuss these issues in detail and summarize the ongoing efforts to reduce the risks of these toxicities.
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Expert Rev Anticancer Ther · Oct 2007
ReviewInflammation and lung carcinogenesis: applying findings in prevention and treatment.
Lung carcinogenesis is a complex process requiring the acquisition of genetic mutations that confer the malignant phenotype as well as epigenetic alterations that may be manipulated in the course of therapy. Inflammatory signals in the lung cancer microenvironment can promote apoptosis resistance, proliferation, invasion, metastasis, and secretion of proangiogenic and immunosuppressive factors. Here, we discuss several prototypical inflammatory mediators controlling the malignant phenotype in lung cancer. ⋯ Inflammatory mediators within the tumor microenvironment are derived from neoplastic cells as well as stromal and inflammatory cells; thus, lung cancer develops in a host environment in which the deregulated inflammatory response promotes tumor progression. Inflammation-related metabolic and catabolic enzymes (prostaglandin E(2) synthase, prostaglandin I(2) synthase and 15-hydroxyprostaglandin dehydrogenase), cell-surface receptors (E-type prostaglandin receptors) and transcription factors (ZEB1, SNAIL, PPARs, STATs and NF-kappaB) are differentially expressed in lung cancer cells compared with normal lung epithelial cells and, thus, may contribute to tumor initiation and progression. These newly discovered molecular mechanisms in the pathogenesis of lung cancer provide novel opportunities for targeted therapy and prevention in lung cancer.
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Lung cancer remains the leading cause of malignancy-related deaths in the USA, regardless of advances in therapeutic agents. Non-small-cell lung cancer demonstrates great molecular heterogeneity in which several pathways are simultaneously active leading to tumorigenesis. Novel agents targeting specific pathways associated with apoptosis, cell proliferation, angiogenesis and other mechanisms have emerged as a separate and unique therapeutic class delivering promising results in a vast number of malignancies. ⋯ Most of these agents have been shown to be 'cytostatic', inducing more stable disease rather than objective responses. Thus, the entrance of these novel agents into our drug armamentarium seems to be more attractive in combination with conventional chemotherapy agents based on additive or synergistic response seen with this combined approach. Herein, we review the most relevant clinical data using these novel targeted agents either alone or in combination with chemotherapy in non-small-cell lung cancer.