Expert review of anticancer therapy
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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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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.
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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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Expert Rev Anticancer Ther · Aug 2007
The Breast Health Global Initiative: clinical practice guidelines for management of breast cancer in low- and middle-income countries.
Breast cancer is an increasingly urgent problem in low- and mid-level resource countries of the world. Despite knowing the optimal management strategy based on guidelines developed in wealthy countries, clinicians are forced to provide less-than-optimal care to patients when diagnostic and/or treatment resources are lacking. For this reason, it is important to identify which resources commonly applied in resource-abundant countries most effectively fill the healthcare needs in limited-resource regions, where patients commonly present with more advanced disease at diagnosis, and to provide guidance on how new resource allocations should be made in order to maximize improvement in outcome. ⋯ The BHGI collaborated with 12 national and international health organizations, cancer societies and nongovernmental organizations to host two BHGI international summits. The evidence-based BHGI Guidelines, developed at the 2002 Global Summit, were published in 2003 as a theoretical treatise on international breast healthcare. These guidelines were then updated and expanded at the 2005 Global Summit into a fully comprehensive and flexible framework to permit incremental improvements in healthcare delivery, based upon outcomes, cost, cost-effectiveness and use of healthcare services.