The Mount Sinai journal of medicine, New York
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New-drug approvals have remained roughly constant since 1950, while the cost of drug development has soared. It seems likely that a more modular approach to drug discovery and development will evolve, deriving some features from the not-for-profit sector. ⋯ These developments, likely prompted by the perception of crisis rather than opportunity, will require linked initiatives among academia, the pharmaceutical industry, the US National Institutes of Health, and the US Food and Drug Administration, along with a more adventurous role for venture capital. A failure to respond threatens the United States' lead in biomedical science and in the development and regulation of novel therapeutics.
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The drug discovery and development enterprise, traditionally an industrial juggernaut, has spanned into the academic arena that is partially motivated by the National Institutes of Health Roadmap highlighting translational science and medicine. Because drug discovery and development represents a pipeline of basic to clinical investigations, it meshes well with the "bench to the bedside" prime directive of translational medicine. ⋯ One area that has received limited attention concerns the use of pharmacokinetic and pharmacodynamic studies in the drug-development process. Using anticancer drug development as a focus, this review will address past and current deficencies in how pharmacokinetic/pharmacodynamic studies are conducted and offer new strategies that might bridge the gap between preclinical and clinical trials.
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Over the past 2 decades, our increased understanding of tumor biology has resulted in the delivery of a new generation of molecularly targeted cancer drugs with greater efficacy and less toxicity. This understanding has also provided pharmaceutical and academic institutions with a greater appreciation for the complexities and challenges associated with discovering and developing molecularly targeted drugs. ⋯ Cooperative efforts by industry and academia have also provided important insights to optimize the use of such agents in the clinic. This review aims to emphasize the need for academic/industrial collaborations for success and efficiency through the drug discovery and development continuum, and will highlight several examples of collaborations between academic and industrial scientists that facilitated the development of molecularly targeted antitumor agents into the clinic.
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Family members used as patients' interpreters are a common occurrence in the medical environments of multicultural societies. It is recognized that the use of the family-member interpreter may have some benefits. ⋯ While numerous studies have been done on the challenges in the doctor-interpreter-patient medical encounter, these studies tend to focus on the experiences of the physicians or the patients, and the perspective of the interpreter is often sidelined. After discussing the various interpreting options, we suggest that the perspective of the family-member interpreter strengthens assertions that professional interpretation is the best option for multilingual medical environments.
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G-protein-coupled receptors are important molecular targets in drug discovery. These receptors play a pivotal role in physiological signaling pathways and are targeted by nearly 50% of currently available drugs. Mounting evidence suggests that G-protein-coupled receptors form dimers, and various studies have shown that dimerization is necessary for receptor maturation, signaling, and trafficking. ⋯ Such antibodies could be used as tools for characterization of heteromer-specific function; as reagents for their purification, tissue localization, and regulation in vivo; and as probes for mapping their functional domains. In addition, such antibodies could serve as alternative ligands for G-protein-coupled receptor heteromers. Thus, heteromer-specific antibodies represent novel tools for the exploration and manipulation of G-protein-coupled receptor-dimer pharmacology.