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本帖最后由 细胞海洋 于 2010-6-19 19:28 编辑 * h8 w- d5 g n9 t5 y/ l% `
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Preface- I$ F5 B, v/ w% G, ]$ [4 i
During the last few years we have seen fundamental changes in the way2 V" o% v! S# l6 S$ Z1 U
scientists approach the identification and validation of new drug targets. These
2 u6 F; G5 [/ j; o8 ~7 J" t. Gnovel strategies for target validation are expected to maximize the likelihood% B J8 F' U1 [* k/ b2 Q8 a# r9 K
of achieving target-selective inhibition with minimal in vivo side effects. For- H( d5 M2 `1 R) F. a7 m6 j
example, by the use of small interfering RNAs (siRNAs) to down regulate9 \; h$ e" X% \5 F* S* c
expression of known genes, a number of therapeutic targets have been validated
# S9 X: A' k% ]/ \/ K+ E" Bboth in vitro and in vivo. The technologies developed to do this have not only
5 S R3 q8 l1 q0 P1 a, v9 Oyielded a significant number of drug targets but have influenced our understanding
' ]2 I+ g4 m5 |4 J( oof gene function, the molecular mechanisms of diseases, and the
3 I) w4 j' a( P% g) K2 _design of new therapeutic interventions. Specific gene and protein targets—on" c& W2 q$ N3 R1 s# C3 q) d- A
which, for example, cancer cells depend—can now be identified, along with \5 _3 X& B8 g7 U' r2 m' ^, W U
the therapeutic agents directed against them. Several relevant examples that
# L N F: [8 a* p" A+ w# M( u+ g2 {( ^have been validated, and some that have reached the clinic, are featured in, F6 r& J3 E5 z4 J: `
Volume 2, Emerging Molecular Drug Targets and Treatment Options, of2 x7 |! a" A4 \9 t
Target Discovery and Validation Reviews and Protocols.
+ V8 S* D% k# dDespite knowing the molecular mechanisms of most drugs, patients vary in h& R+ M# R0 m( C. e8 i w# U
their responses to a medication’s efficacy and side effects. Indeed, the sequence2 c# [& H" i; ~6 y5 Y! h4 k0 i }
of the human genome has shown that there is extensive genetic variation among
( J8 L, @/ a$ _! b. Uindividuals that would be expected to affect the response to medication. Thus,
" s4 B* g0 _' `# ]) j8 [a better understanding of the molecular mechanisms that lead to an improved
5 v7 X1 u. a/ Z5 e% u `treatment response should play an important role in the development of
! j! w! g- O+ Z. zindividualized medicine. DNA sequence alterations and the expression profiles
/ G# U2 @0 H) ?of mRNA molecules and proteins can be used to predict drug response. These# B8 A& `+ J; l- O$ ?" ~! d) d
genetic and epigenetic changes may be used in turn to develop treatment$ E. u: z1 \" @6 X2 p- h6 J
algorithms adjusted for use in individual patients. Several examples of such
5 d' h) j1 e; r3 xindividualized treatment, aimed at increasing drug efficacy as well as- s& i3 l. [; y" x1 s! j) V
decreasing toxicity, are discussed in this edition.
+ k' h: O+ C, ?' c! E0 r7 i& xIn systemic autoimmune diseases, current clinical practice calls for
! V: X; K/ {2 F: @immunosuppressive drug therapy. However, some drugs are not target-specific
' d7 b* v% y8 b; {and some carry a high risk of side effects. New immunosuppressive strategies,! U$ D5 M' e$ E) K! T G
such as monoclonal antibodies and receptor antagonists, are now emerging as, Z. Z6 h# A: x4 W; r
potentially valuable discriminating agents for use in innovative combinations.* Q4 Q; Q& g! E% A! d* L
Such novel opportunities for therapeutic targeting in systemic autoimmune
% Z+ S6 U" Q( B p' }! fdiseases are described in Volume 2.
" b7 @+ u- A8 L5 DMicroRNAs (miRNAs) are a family of short noncoding regulatory RNA
7 e# U, O9 W3 amolecules expressed in a variety of different cell types. These tiny RNAs have# t9 c+ I$ Q1 T* z0 ^, Q! Z
been shown to play important biological functions and may regulate the
. I7 O3 ?( F; i U& m, G, qexpression of more than 30% of human genes. Presently, evidence is emerging/ `' t* G# B3 C1 _
that particular miRNAs may play a role in human cancer pathogenesis. Thus,
8 i$ D( B4 D4 O* gthe identification of miRNA expression signatures in patients with cancer may
$ e0 g. `, N* f/ U3 `$ x& A, S+ ehelp to identify subjects who are at high risk of developing cancer or those who
+ p' V: W. _8 X. i, s+ I) @have an early stage of cancer. In order to interfere with miRNA expression,% ~9 \" w. J& J
modified antisense oligonucleotides targeting individual miRNAs have been
0 a" D* X, x' ? K- B/ B1 rdeveloped and these agents have the potential to eventually progress into a
- O$ W. I6 K- N$ q' Enew class of therapeutic agents.
9 y- V# b0 v1 q- K& VVolume II, Emerging Molecular Drug Targets and Treatment Options, was
) {9 B# t7 @( Y( M4 Swritten by leading experts in the field and presents a unique source of current
) Q7 p. @: f$ }5 ?" minformation. Along with Volume I, Emerging Strategies in Drug Targets and
* [! d% Q5 H/ l1 Q1 B3 H; z$ eBiomarker Discovery, this work will be of interest to researchers, pharmaceutical
9 }6 @- l T3 ^, n$ g8 Scompanies, clinicians, and students of biology, medicine, or pharmacy.1 p9 p3 ]! n. I. m8 {0 L
I would like to thank the authors for their contributions, Anne Dybwad for% y( `& X/ u7 ^0 _- V: O; T. a* m
critical reading of the manuscripts, and all those involved in the production of- z- Z" S' ?9 K) M! k ~
the book.( O, q7 c4 X% f) T0 U7 K- ?8 T
Mouldy Sioud1 w) j# w; v6 x- b( V0 J- _
8 O, D* r4 v' |( H7 T+ J[hide][/hide] |
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发表于 2010-6-19 18:53
发表于 2010-6-20 10:45
