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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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- s5 l1 y& x+ l, K3 g" oPreface3 { w# ^) y" Z/ n5 c
During the last few years we have seen fundamental changes in the way
4 ~& |* N h: E5 c! Z3 Xscientists approach the identification and validation of new drug targets. These: g' n5 z& L; `4 w4 m. X
novel strategies for target validation are expected to maximize the likelihood
2 s! e2 t8 Z2 x% v" w$ ?; ]$ M' sof achieving target-selective inhibition with minimal in vivo side effects. For
, h9 ^- j% W( {+ w2 @example, by the use of small interfering RNAs (siRNAs) to down regulate' g7 N7 P7 J% ]5 q" }, j1 F
expression of known genes, a number of therapeutic targets have been validated6 G k+ j; _3 \
both in vitro and in vivo. The technologies developed to do this have not only
8 F( x& w3 W) ]$ Y$ `yielded a significant number of drug targets but have influenced our understanding
5 o7 r, r* s; Z9 z# q" J$ l) n' wof gene function, the molecular mechanisms of diseases, and the
) J( a4 r; [) k6 S, c6 l: B" Mdesign of new therapeutic interventions. Specific gene and protein targets—on- m; ^$ l" a+ h5 d# x: b
which, for example, cancer cells depend—can now be identified, along with
, J5 J9 A/ ~: N: D- Mthe therapeutic agents directed against them. Several relevant examples that
* [3 p% i/ r( r8 m d. E6 ]have been validated, and some that have reached the clinic, are featured in0 B% O/ g, R( w4 n% E; T
Volume 2, Emerging Molecular Drug Targets and Treatment Options, of/ G* T5 f! z* q( Z) X- P
Target Discovery and Validation Reviews and Protocols." W9 y" G( d% l/ r* g: C, E
Despite knowing the molecular mechanisms of most drugs, patients vary in; _: Z8 ~- ^8 h0 l: n
their responses to a medication’s efficacy and side effects. Indeed, the sequence8 y, S8 C9 q; c; h
of the human genome has shown that there is extensive genetic variation among
) r8 u o2 z( L8 _ windividuals that would be expected to affect the response to medication. Thus,
, Y: x5 _6 _) M% j" Za better understanding of the molecular mechanisms that lead to an improved" t L8 T: ~- v5 i
treatment response should play an important role in the development of
- e0 w) g, }. m; Z; \* ~individualized medicine. DNA sequence alterations and the expression profiles2 S( t- F. b' H. f }$ d
of mRNA molecules and proteins can be used to predict drug response. These
. k( x7 a3 W3 W G C: ~) z$ v% L0 jgenetic and epigenetic changes may be used in turn to develop treatment' m$ m8 o$ i( L. h
algorithms adjusted for use in individual patients. Several examples of such9 t" z1 p: P7 ^6 ?6 M
individualized treatment, aimed at increasing drug efficacy as well as
2 A% y+ @4 e& D/ _( y# Hdecreasing toxicity, are discussed in this edition.
" n1 z w6 L2 o1 R& \9 m8 y7 yIn systemic autoimmune diseases, current clinical practice calls for
8 r: c1 F0 L0 F6 _1 D jimmunosuppressive drug therapy. However, some drugs are not target-specific
: j8 Q) s5 k @: {) x! land some carry a high risk of side effects. New immunosuppressive strategies,
& m+ [, Y7 m6 I- k* W* }such as monoclonal antibodies and receptor antagonists, are now emerging as/ V- F) s7 M2 i3 R
potentially valuable discriminating agents for use in innovative combinations.5 v. f2 N* K$ K8 c" K
Such novel opportunities for therapeutic targeting in systemic autoimmune9 r- P4 i. @% S# Y3 d
diseases are described in Volume 2.
3 @/ q% T0 [8 RMicroRNAs (miRNAs) are a family of short noncoding regulatory RNA
" E3 @! h Z% F6 q$ B; Gmolecules expressed in a variety of different cell types. These tiny RNAs have
* S S- J, B6 x1 L& ibeen shown to play important biological functions and may regulate the& ]( T" Q( d( d
expression of more than 30% of human genes. Presently, evidence is emerging
7 O' ?. }! m6 H3 f' h Y4 s+ Mthat particular miRNAs may play a role in human cancer pathogenesis. Thus,
. X; |# j! X- l2 x9 U/ E9 q9 Lthe identification of miRNA expression signatures in patients with cancer may. F6 M+ L& R; Z; A
help to identify subjects who are at high risk of developing cancer or those who2 W% ~- y0 _ e4 V/ a/ h5 @
have an early stage of cancer. In order to interfere with miRNA expression,
. J, P6 |1 f! E6 T$ b8 Omodified antisense oligonucleotides targeting individual miRNAs have been9 N$ d# K! `2 ^& Z1 o' Y
developed and these agents have the potential to eventually progress into a" v9 o# w0 J: U9 C# u
new class of therapeutic agents.
( g) E+ v" `2 ?6 }1 j4 ?Volume II, Emerging Molecular Drug Targets and Treatment Options, was
, F8 Y% O- v/ H- p' Owritten by leading experts in the field and presents a unique source of current( Z9 Y8 G2 t3 |6 ?
information. Along with Volume I, Emerging Strategies in Drug Targets and
" @) W$ r8 A( pBiomarker Discovery, this work will be of interest to researchers, pharmaceutical' l) }6 k& R i0 o+ }( Y
companies, clinicians, and students of biology, medicine, or pharmacy.# o) b3 ~8 [4 q! O. [' ^
I would like to thank the authors for their contributions, Anne Dybwad for* Z2 `: S8 I. Y1 Z, Q% I, G
critical reading of the manuscripts, and all those involved in the production of- B8 c% R3 I9 S1 c$ M, y4 c
the book.1 r0 b: M$ Z! I) V1 d) O$ U- s+ c; ~
Mouldy Sioud8 K" N. Q; n |; m4 ?
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发表于 2010-6-19 18:53
