标题: PDF电子书：Target Discovery and Validation Reviews and Protocols—2 [打印本页] 作者: lifescience1 时间: 2010-6-19 18:53 标题: PDF电子书：Target Discovery and Validation Reviews and Protocols—2
本帖最后由 细胞海洋 于 2010-6-19 19:28 编辑 , b$ S; q; P% A
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[attach]9464[/attach] 7 t8 e/ [5 R2 e4 A& }: C7 Z- V TPreface 8 w. H: v4 E: b5 F" e& wDuring the last few years we have seen fundamental changes in the way2 }6 l5 }5 ]- K3 ?2 |: k$ @4 W
scientists approach the identification and validation of new drug targets. These + ~1 H w6 f) }8 [novel strategies for target validation are expected to maximize the likelihood9 I' [8 @0 h) D
of achieving target-selective inhibition with minimal in vivo side effects. For# T4 H) G% `4 u+ K. J
example, by the use of small interfering RNAs (siRNAs) to down regulate 5 [( r3 H7 G9 M- ^* u: M* kexpression of known genes, a number of therapeutic targets have been validated 9 T- v% Z, c. ]; Aboth in vitro and in vivo. The technologies developed to do this have not only 6 \# V3 n. F5 U+ T4 Q, hyielded a significant number of drug targets but have influenced our understanding; S% I9 G F0 k" x7 N- R
of gene function, the molecular mechanisms of diseases, and the$ S; [7 U2 G4 `6 E3 c
design of new therapeutic interventions. Specific gene and protein targets—on ( c3 Y6 F( A3 P9 \8 ~$ u, Cwhich, for example, cancer cells depend—can now be identified, along with # l9 j3 b1 ^/ P8 q4 U othe therapeutic agents directed against them. Several relevant examples that5 H4 J+ j* Y8 |: }: z+ r
have been validated, and some that have reached the clinic, are featured in: t( Q! i8 L. k; P, R& s
Volume 2, Emerging Molecular Drug Targets and Treatment Options, of 8 Q2 Q: G) q% j" O0 b h0 KTarget Discovery and Validation Reviews and Protocols., [. i- [, K" }, N7 Z( V+ Z2 J7 I
Despite knowing the molecular mechanisms of most drugs, patients vary in% f& s x9 e- h
their responses to a medication’s efficacy and side effects. Indeed, the sequence 6 {. S, W0 q/ B8 W+ A4 j1 Tof the human genome has shown that there is extensive genetic variation among . Z! W; {0 N1 g. ]! q6 dindividuals that would be expected to affect the response to medication. Thus, , w- c, a8 T- t0 [. K% p& H5 y0 ea better understanding of the molecular mechanisms that lead to an improved4 b+ e; x3 M7 x/ ^
treatment response should play an important role in the development of * Z6 n7 m r, n5 U' tindividualized medicine. DNA sequence alterations and the expression profiles 6 }0 U- h6 q F9 f4 e6 K hof mRNA molecules and proteins can be used to predict drug response. These, e2 p8 V. o; ~) Q$ ^2 [$ m
genetic and epigenetic changes may be used in turn to develop treatment) e# P6 ~+ j3 I- t, S
algorithms adjusted for use in individual patients. Several examples of such ; W/ N0 W# v; u0 U2 \" `8 f) sindividualized treatment, aimed at increasing drug efficacy as well as" r6 o6 [' `0 h- b' S. p* n
decreasing toxicity, are discussed in this edition.( K( _; p+ J1 G$ z5 e2 t
In systemic autoimmune diseases, current clinical practice calls for ) z, J- F9 R9 B/ @- z+ K' \# X8 ?immunosuppressive drug therapy. However, some drugs are not target-specific ; ~6 @, S4 `* M! C) P% o' D$ Kand some carry a high risk of side effects. New immunosuppressive strategies, 5 N6 X3 l& l0 jsuch as monoclonal antibodies and receptor antagonists, are now emerging as ; k- n* G1 }; f( j# g) `& M/ bpotentially valuable discriminating agents for use in innovative combinations.! ~, ^: u& i8 H, T/ ?6 Z
Such novel opportunities for therapeutic targeting in systemic autoimmune+ F+ t q5 H# B, `+ Y
diseases are described in Volume 2. 5 r! x+ O3 e' d" L4 OMicroRNAs (miRNAs) are a family of short noncoding regulatory RNA 9 m' s! o4 Y' zmolecules expressed in a variety of different cell types. These tiny RNAs have1 a C0 N: n" O# o* i
been shown to play important biological functions and may regulate the+ E9 ~7 u( Q+ I* r9 m
expression of more than 30% of human genes. Presently, evidence is emerging * k+ T+ U2 D. ^ Z+ q! rthat particular miRNAs may play a role in human cancer pathogenesis. Thus, 7 v6 `( b! V3 Z4 E" ?8 D$ H/ Sthe identification of miRNA expression signatures in patients with cancer may & |* R% o6 {9 o& N. jhelp to identify subjects who are at high risk of developing cancer or those who 7 m* z( w( P$ G" Zhave an early stage of cancer. In order to interfere with miRNA expression, 4 O* i \$ R/ c- n4 h' Jmodified antisense oligonucleotides targeting individual miRNAs have been $ O* P+ \" X- t; X! E; k! T+ J4 A; `developed and these agents have the potential to eventually progress into a3 u m X* d0 G: D7 E4 V: q& o
new class of therapeutic agents. - z: W0 z8 a: ~' M, {- o$ y0 [Volume II, Emerging Molecular Drug Targets and Treatment Options, was : `5 r: \9 ?/ b: c; Fwritten by leading experts in the field and presents a unique source of current / S- _+ G2 q" B- X$ f8 S$ t- _information. Along with Volume I, Emerging Strategies in Drug Targets and, ?, ^3 ]; t" N6 i8 N# ?6 L
Biomarker Discovery, this work will be of interest to researchers, pharmaceutical , A5 n/ ?' Z6 Z( Zcompanies, clinicians, and students of biology, medicine, or pharmacy. }" s* X2 V1 _! KI would like to thank the authors for their contributions, Anne Dybwad for9 y+ u5 l' v* ^ y
critical reading of the manuscripts, and all those involved in the production of: j7 Q9 j' e) y y
the book.: F. @) a( w |3 t
Mouldy Sioud' h5 Z: v5 C9 g8 n+ m1 a' v