Topic_1_AAAAkonstantinopoulos_etal_2009 - Educational and...

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60 | KONSTANTINOPOULOS ET AL. | MOL MED 15(1-2)60-63, JANUARY-FEBRUARY 2009 Molecular medicine is transforming everyday clinical practice in an unprece- dented manner (1). Oncologists treat RAS -mutated non-small cell lung cancer, hematologists encounter T315I-mutation chronic myelogenous leukemia, patholo- gists recognize activated B-cell-like dif- fuse large B-cell lymphoma, primary care physicians follow BRCA1 or BRCA2 mu- tation carriers, infectious disease doctors treat different hepatitis C virus (HCV)- genotypes, and cardiologists will soon be using organic anion transporting polypep- tide 1B1 ( SLCO1B1 ) polymorphisms for tailoring statin therapy (2). Molecular medicine originates from the results of biomedical research aimed at decoding the cellular and molecular mechanisms involved in human health and disease with the ultimate goal of redefining and reclassifying disease states and condi- tions on a strictly etiological basis. The evolution of technologies targeting the genome (polymerase chain reaction [PCR], comparative genomic hybridiza- tion, single nucleotide polymorphism ar- rays) or the transcriptome (real time quantitative PCR, mRNA, and mi- croRNA expression arrays) facilitate opti- mized, individualized management of patients. As a result, therapeutic efficacy is maximized by selecting drugs target- ing genetically defined patient subpopu- lations and disease subtypes, while toxic- ity is circumvented by avoiding treatment in patients predicted to derive no benefit, experience significant toxicity, or have excellent prognosis, regardless of therapy. Thus, the prevailing concept in the emerging framework of molecular medicine is a personalized approach to disease prevention, diagnosis, prognosis, and treatment. Furthermore, the detailed knowledge of molecular pathophysiol- ogy has enabled identification of novel strategies—”novel concepts”—for drug development as exemplified by exploita- tion of oncogenic addiction (that is, de- velopment of epidermal growth factor receptor [EGFR] inhibitors in non-small cell lung cancer) or synthetic lethality (that is, development of poly[ADP- ribose] polymerase [PARP] inhibitors in homologous recombination repair defi- cient tumors) in cancer therapy (3,4). The translation of the advances of mo- lecular medicine into clinical practice is not without technical, educational, as well as social-ethical, challenges. Al- though the application of genomic tech- nologies into discovery of new disease classifications on the basis of novel ge- netic and epigenetic alterations has been highly successful, application of tech- nologies targeting the transcriptome has yet to contribute much to the day-to-day care of patients. While a large body of lit- erature has described multi-gene expres- sion profiles potentially useful for dis- ease classification, diagnosis, and prognosis (5), only a few of these discov- eries have been validated independently
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This note was uploaded on 11/26/2010 for the course IB 35AC taught by Professor Hlusko during the Spring '08 term at Berkeley.

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Topic_1_AAAAkonstantinopoulos_etal_2009 - Educational and...

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