ISSN:1175-2203    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

The concept of personalized medicine – that medical care can be tailored to the genomic and molecular profile of the individual – has repercussions that extend far beyond the technology that makes it possible. The adoption of personalized medicine will require changes in healthcare infrastructure, diagnostics and therapeutics business models, reimbursement policy from government and private payers, and a different approach to regulatory oversight. Personalized medicine will shift medical practices upstream from the reactive treatment of disease, to proactive healthcare management including screening, early treatment, and prevention, and will alter the roles of both physician and patient. It will create a greater reliance on electronic medical records and decision support systems in an industry that has a long history of resistance to information technology.Personalized medicine requires a systems approach to implementation. But in a healthcare economy that is highly decentralized and market driven, it is incumbent upon the stakeholders themselves to advocate for a consistent set of policies and legislation that pave the way for the adoption of personalized medicine. To address this need, the Personalized Medicine Coalition (PMC) was formed as a nonprofit umbrella organization of pharmaceutical, biotechnology, diagnostic, and information technology companies, healthcare providers and payers, patient advocacy groups, industry policy organizations, major academic institutions, and government agencies. The PMC provides a structure for achieving consensus positions among these stakeholders on crucial public policy issues, a role which will be vital to translating personalized medicine into widespread clinical practice.In this article, we outline the goals of the PMC, and the strategies it will take to foster communication, debate, and consensus on issues such as genetic discrimination, the reimbursement structures for pharmacogenomic drugs and diagnostics, regulation, physician training and medical school curricula, and public education.

ISSN:1175-2203    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

A new diagnostic tool must pass three major tests before it is adopted for routine clinical use. First, the tool must be robust and reproducible; second, the clinical value of the tool must be proven, i.e. the tool should reliably trigger a clinical decision that results in patient benefit; and, third, the clinical community has to be convinced of the need for this tool and the benefits it affords. Another factor that can influence the adoption of new tools relates to the cost and the vagaries of insurance reimbursement.The Cancer Diagnosis Program (CDP) of the US National Cancer Institute (NCI) launched the Program for the Assessment of Clinical Cancer Tests (PACCT) in 2000 to develop a process for moving the results of new technologies and new understanding of cancer biology more efficiently and effectively into clinical practice. PACCT has developed an algorithm that incorporates the iterative nature of assay development into an evaluation process that includes developers and end users. The effective introduction of new tests into clinical practice has been hampered by a series of common problems that are best described using examples of successes and failures.The successful application of the PACCT algorithm is described in the discussion of the recent development of the OncotypeDX™ assay and plan for a prospective trial of this assay by the NCI-supported Clinical Trials Cooperative Groups. The assay uses reverse transcription (RT)-PCR evaluation of a set of 16 genes that were shown to strongly associate with the risk of recurrence of breast cancer in women who presented with early stage disease (hormone responsive, and no involvement of the auxiliary lymph nodes). The test is highly reproducible. It provides information to aid the physician and patient in making important clinical decisions, including the aggressiveness of the therapy that should be recommended. A trial is planned to test whether OncotypeDX™ can be used as a standalone trigger for specific treatment decisions.The problems that have been encountered and have delayed the development of other diagnostic tools are exemplified in the development of tests for human epidermal growth factor receptor (HER2) overexpression, for predictors of response to epidermal growth factor receptor inhibitors, and for the detection of residual disease following chemotherapy.

ISSN:1175-2203    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Genomic-based methodologies are increasingly used at all stages of drug development. The most extensive applications have occurred in early drug discovery stages due to advances in technologies that allow for automated synthesis and characterization of organic compounds, and for high-throughput screening of these molecules against known drug targets. The adaptation of genomic-based methodologies in later stages of drug development presents a more difficult task.In this review we describe how genomics can be used to identify previously uncharacterized pharmacologic actions that provide a basis for the development of new classes of antimycotic agents or for adverse event aversion. Clinically, novel antimycotics are gravely needed. This review provides a perspective on new technologies that will bridge the gap between drug discovery and development that may enable more rapid access to new antimycotic agents.

ISSN:1175-2203    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Genomics and proteomics technologies have created a paradigm shift in the drug discovery process, with bioinformatics having a key role in the exploitation of genomic, transcriptomic, and proteomic data to gain insights into the molecular mechanisms that underlie disease and to identify potential drug targets. We discuss the current state of the art for some of the bioinformatic approaches to identifying drug targets, including identifying new members of successful target classes and their functions, predicting disease relevant genes, and constructing gene networks and protein interaction networks. In addition, we introduce drug target discovery using the strategy of systems biology, and discuss some of the data resources for the identification of drug targets.Although bioinformatics tools and resources can be used to identify putative drug targets, validating targets is still a process that requires an understanding of the role of the gene or protein in the disease process and is heavily dependent on laboratory-based work.

ISSN:1175-2203    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

This is the final part of a four-part serial review on oncogenes and their potential use as targets for cancer therapy. Previous sections discussed various categories of oncogenes (growth factors, tyrosine kinases, intermediate signaling molecules, and transcription factors) and the advances made in various strategies being used to alter their actions. This part describes four oncogenes, MDM2, BCL2, XIAP, and Survivin, that are involved in regulation of the cell cycle and apoptosis.

ISSN:1175-2203    

出版商:ADIS    

年代:2005

数据来源: ADIS