! l; D8 o( Y( t. g. t" A3 A! q1 s[attach]9464[/attach] * g. x2 {9 P P) M+ ~Preface ( q2 h: G5 a' ?2 lDuring the last few years we have seen fundamental changes in the way8 B8 r% D1 r; c5 k, }; q) R! L
scientists approach the identification and validation of new drug targets. These ; m7 u$ e: I/ s6 J `, B5 Y# ynovel strategies for target validation are expected to maximize the likelihood3 ?" L* D ]2 D# M- E1 K
of achieving target-selective inhibition with minimal in vivo side effects. For9 O* E4 }# v/ ~. o( |
example, by the use of small interfering RNAs (siRNAs) to down regulate $ X+ H1 V7 r @8 @4 texpression of known genes, a number of therapeutic targets have been validated) m6 D& k: g2 D8 r* |7 d
both in vitro and in vivo. The technologies developed to do this have not only 2 j3 t2 z1 h& M2 Eyielded a significant number of drug targets but have influenced our understanding4 A9 c B$ x5 }$ F! P( N( `
of gene function, the molecular mechanisms of diseases, and the O1 r, o- n5 z+ a: [design of new therapeutic interventions. Specific gene and protein targets—on + ~: f8 x% |: e( n& S1 d& Mwhich, for example, cancer cells depend—can now be identified, along with * X9 T" u' N% Vthe therapeutic agents directed against them. Several relevant examples that 9 R8 B @# K; O" h3 Ahave been validated, and some that have reached the clinic, are featured in " @% i! e( R, _Volume 2, Emerging Molecular Drug Targets and Treatment Options, of6 W0 q4 U& d, a' t
Target Discovery and Validation Reviews and Protocols. - g( R/ k+ x* Z9 \2 b1 q! G+ yDespite knowing the molecular mechanisms of most drugs, patients vary in 6 t, m9 }& h: P- m1 [their responses to a medication’s efficacy and side effects. Indeed, the sequence" s: m9 E$ S" S5 M+ i# s: [
of the human genome has shown that there is extensive genetic variation among 1 v: y; _! R3 zindividuals that would be expected to affect the response to medication. Thus,! `5 Q X9 u) \' N9 Z
a better understanding of the molecular mechanisms that lead to an improved- j' S+ y* Z+ Y
treatment response should play an important role in the development of# t1 p% \5 T. d/ G4 [& [
individualized medicine. DNA sequence alterations and the expression profiles5 g; t& H) ^) T/ P5 E8 y
of mRNA molecules and proteins can be used to predict drug response. These . D; Q3 n: p6 o Rgenetic and epigenetic changes may be used in turn to develop treatment, q7 X4 v0 p: d" o$ X* K5 v
algorithms adjusted for use in individual patients. Several examples of such `1 E, i, q W* T+ k2 ^2 u
individualized treatment, aimed at increasing drug efficacy as well as0 B# ?5 n! J# V' q7 X, s/ D
decreasing toxicity, are discussed in this edition. * {1 E0 ~ ^/ X4 j- xIn systemic autoimmune diseases, current clinical practice calls for6 H$ B' y6 ~/ }* S3 C
immunosuppressive drug therapy. However, some drugs are not target-specific , ]& g0 f* k2 R8 [2 Nand some carry a high risk of side effects. New immunosuppressive strategies, ( _% b7 L& p. Y3 Ksuch as monoclonal antibodies and receptor antagonists, are now emerging as ! J$ O8 q9 {1 Z, {potentially valuable discriminating agents for use in innovative combinations. 8 V2 R( C* x! U k% x( c; h( ~Such novel opportunities for therapeutic targeting in systemic autoimmune 7 I* s( Q! w* e Zdiseases are described in Volume 2. 7 |+ Y) _) R+ k! q/ |MicroRNAs (miRNAs) are a family of short noncoding regulatory RNA, Y0 {9 m* K# x1 |. x
molecules expressed in a variety of different cell types. These tiny RNAs have , l( k" R8 w# O( gbeen shown to play important biological functions and may regulate the H' B, b$ g4 \3 m% B8 S
expression of more than 30% of human genes. Presently, evidence is emerging 0 x5 A! x! Z6 S v' d: F7 Vthat particular miRNAs may play a role in human cancer pathogenesis. Thus,0 ] R8 I+ X- O2 a5 T
the identification of miRNA expression signatures in patients with cancer may* P% q" F( Y0 a6 d
help to identify subjects who are at high risk of developing cancer or those who ! p, l" K9 z8 {+ Ihave an early stage of cancer. In order to interfere with miRNA expression, 7 U7 r- F+ Y6 s& e$ ^# Amodified antisense oligonucleotides targeting individual miRNAs have been / M; Z4 y/ ^( G1 T4 N t( T. z+ `developed and these agents have the potential to eventually progress into a& @8 w) j; Q+ U0 t& N9 u
new class of therapeutic agents. 8 O, |4 A' F' N9 \) _: `4 h1 ?4 jVolume II, Emerging Molecular Drug Targets and Treatment Options, was1 P7 B/ D4 X0 \* z+ E6 \
written by leading experts in the field and presents a unique source of current , P3 h! M7 h! `7 Xinformation. Along with Volume I, Emerging Strategies in Drug Targets and : F! q- c4 d0 I% w. U$ E! R+ kBiomarker Discovery, this work will be of interest to researchers, pharmaceutical: _$ c3 E' y1 z, W/ [! d
companies, clinicians, and students of biology, medicine, or pharmacy. 6 P( G5 b$ [. O* ^/ U) X, k' iI would like to thank the authors for their contributions, Anne Dybwad for0 Z$ \4 l& O' k/ B4 J+ O# o
critical reading of the manuscripts, and all those involved in the production of7 S, o3 U! K. | i
the book. " H$ _2 ~5 f2 {& eMouldy Sioud & X8 l% [. @( u3 z0 V# W $ v( F( a# I# B作者: hany2007 时间: 2010-6-19 21:43
谢谢分享作者: sunyucheng 时间: 2010-6-19 22:01
看看作者: wgydys 时间: 2010-6-19 23:05
thanks作者: woosheng 时间: 2010-6-20 08:32
谢谢分享作者: lixiaodong 时间: 2010-6-20 08:43
谢谢。作者: ambassador 时间: 2010-6-20 10:45
新兴的分子靶标及治疗方案！6 s) I4 j0 K7 R; A D
关于癌症治疗的吗？作者: foxp3 时间: 2010-6-20 16:59