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本帖最后由 细胞海洋 于 2010-6-19 19:28 编辑
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Preface0 O' l9 c" w5 {; ^0 U# m
During the last few years we have seen fundamental changes in the way7 F5 h. x; |' M& \$ `4 Q: Y
scientists approach the identification and validation of new drug targets. These
& h* j7 l6 t# ?novel strategies for target validation are expected to maximize the likelihood) Z: a: [9 W& e8 {" ^9 ~3 E3 M) v
of achieving target-selective inhibition with minimal in vivo side effects. For$ E& ^" s: |( Q
example, by the use of small interfering RNAs (siRNAs) to down regulate
2 E! w1 V: T/ g: F5 X0 T3 Yexpression of known genes, a number of therapeutic targets have been validated# q4 ]2 O$ c& K: S
both in vitro and in vivo. The technologies developed to do this have not only
' ^3 V' }1 K0 U: l1 p8 ?& cyielded a significant number of drug targets but have influenced our understanding: x7 h) c$ e; L$ E, K' E
of gene function, the molecular mechanisms of diseases, and the
2 Q+ |+ }! D9 O2 N0 o. k& v- ~+ _design of new therapeutic interventions. Specific gene and protein targets—on
; w1 j F6 M1 S9 m l9 zwhich, for example, cancer cells depend—can now be identified, along with
, S+ L8 W* O' Vthe therapeutic agents directed against them. Several relevant examples that. @8 K1 L Z% z, ~6 l0 {
have been validated, and some that have reached the clinic, are featured in
[2 Q. [7 `- \( \$ [* c, j% N( f+ jVolume 2, Emerging Molecular Drug Targets and Treatment Options, of# g6 T2 d8 n, X7 B1 F
Target Discovery and Validation Reviews and Protocols.
% P8 Q! h$ h4 ^# C* |Despite knowing the molecular mechanisms of most drugs, patients vary in
$ j* h8 i1 M1 S, atheir responses to a medication’s efficacy and side effects. Indeed, the sequence& E1 z1 R; ~, I+ s
of the human genome has shown that there is extensive genetic variation among n B8 k' B$ Q3 V. C: r# _2 b# h
individuals that would be expected to affect the response to medication. Thus,+ y+ M8 j) P2 t2 n9 Z) q6 K8 a
a better understanding of the molecular mechanisms that lead to an improved) d% q9 C- `8 \3 l
treatment response should play an important role in the development of
' A+ e3 M0 ~% ?- i- |individualized medicine. DNA sequence alterations and the expression profiles
5 Y" v: ?( M+ R: Nof mRNA molecules and proteins can be used to predict drug response. These
: x9 p0 v; @& G: x6 O5 y: v2 N9 O8 Vgenetic and epigenetic changes may be used in turn to develop treatment0 @& N. t% c* s# u* G
algorithms adjusted for use in individual patients. Several examples of such' _! ~% [5 M! N& e
individualized treatment, aimed at increasing drug efficacy as well as9 B3 m6 Q( ~, p% h/ v* H, R
decreasing toxicity, are discussed in this edition.
8 E% W6 y4 r6 ]5 g- K2 P- cIn systemic autoimmune diseases, current clinical practice calls for
& t, i; o& o/ @ E5 T) Limmunosuppressive drug therapy. However, some drugs are not target-specific
# N$ b8 J$ n1 O& [and some carry a high risk of side effects. New immunosuppressive strategies,
# g7 H% l1 G- f% Csuch as monoclonal antibodies and receptor antagonists, are now emerging as
' F8 _( C d% P1 K& n4 apotentially valuable discriminating agents for use in innovative combinations.1 Z- ~3 H3 _+ D' g }1 u
Such novel opportunities for therapeutic targeting in systemic autoimmune
9 A+ o% t- I% D, K1 _diseases are described in Volume 2.0 M& J6 v, h) f( I
MicroRNAs (miRNAs) are a family of short noncoding regulatory RNA( _% _5 L; W7 {7 c
molecules expressed in a variety of different cell types. These tiny RNAs have+ i9 A' r0 `' S, c
been shown to play important biological functions and may regulate the1 T `# v+ q5 U" `8 X2 p7 Z5 i
expression of more than 30% of human genes. Presently, evidence is emerging' _; D) s. c- a. ?' b1 _7 ~ L. b
that particular miRNAs may play a role in human cancer pathogenesis. Thus,: R9 W# @3 _" F5 I& [2 m
the identification of miRNA expression signatures in patients with cancer may# Q! T6 \! P* `# a$ |4 e% P
help to identify subjects who are at high risk of developing cancer or those who" B1 R7 a% n' {# K- d5 r! I
have an early stage of cancer. In order to interfere with miRNA expression,
3 k3 w' j- o+ R6 { t. f8 q$ S( |/ {5 `modified antisense oligonucleotides targeting individual miRNAs have been
6 q. P* X# r1 C2 x0 w# zdeveloped and these agents have the potential to eventually progress into a2 x0 \3 E* \4 I$ ]! r+ K- ?
new class of therapeutic agents. X3 K- k; _! T( U
Volume II, Emerging Molecular Drug Targets and Treatment Options, was5 ?: L$ K2 \8 m
written by leading experts in the field and presents a unique source of current
2 R6 P3 r" N' finformation. Along with Volume I, Emerging Strategies in Drug Targets and' Q6 D* X# m9 g
Biomarker Discovery, this work will be of interest to researchers, pharmaceutical
% ]5 }5 \8 d. X- i$ ^6 qcompanies, clinicians, and students of biology, medicine, or pharmacy.
3 |- @, ]; D- Z, U0 P/ Y. ?I would like to thank the authors for their contributions, Anne Dybwad for- A% P- H/ U( O
critical reading of the manuscripts, and all those involved in the production of; M( `8 x% W9 u3 {9 z7 H9 V
the book.+ c9 s- [; b, l# ~# T, {! q
Mouldy Sioud
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发表于 2010-6-19 18:53
发表于 2010-6-20 10:45
