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发表于 2010-6-19 18:53 |只看该作者 |倒序浏览 |打印

本帖最后由细胞海洋于 2010-6-19 19:28 编辑 8 S% W0 ]6 B9 }9 S; F$ X, T5 ~2 W

Preface: C3 Z9 J$ L3 a# d4 ]5 P: M  M) E
During the last few years we have seen fundamental changes in the way
scientists approach the identification and validation of new drug targets. These
novel strategies for target validation are expected to maximize the likelihood
of achieving target-selective inhibition with minimal in vivo side effects. For& }; L& ~8 i8 ^/ e; s
example, by the use of small interfering RNAs (siRNAs) to down regulate! c$ G$ f% `' P& t4 V( c
expression of known genes, a number of therapeutic targets have been validated9 @  |; Q# R% u( i0 E
both in vitro and in vivo. The technologies developed to do this have not only; e0 m) N4 B5 D6 s  M
yielded a significant number of drug targets but have influenced our understanding/ J4 d2 w: O" W5 \3 g
of gene function, the molecular mechanisms of diseases, and the
design of new therapeutic interventions. Specific gene and protein targets—on2 F/ z9 w, Z4 s1 X3 `: e
which, for example, cancer cells depend—can now be identified, along with. P) _% i( X6 t/ `  g' N7 T
the therapeutic agents directed against them. Several relevant examples that4 x1 I3 `6 P/ f' T4 z2 f
have been validated, and some that have reached the clinic, are featured in
Volume 2, Emerging Molecular Drug Targets and Treatment Options, of2 y2 O& I" v2 W3 E) k# o2 g, }/ e
Target Discovery and Validation Reviews and Protocols.
Despite knowing the molecular mechanisms of most drugs, patients vary in- ?" P) U5 R8 \. j: e/ Y
their responses to a medication’s efficacy and side effects. Indeed, the sequence( E/ Z/ n4 ~* a( X/ n! O6 B' D
of the human genome has shown that there is extensive genetic variation among! m* Y2 G! g" _4 M' P' o% E
individuals that would be expected to affect the response to medication. Thus,$ Y, ]2 P7 |3 S, J
a better understanding of the molecular mechanisms that lead to an improved
treatment response should play an important role in the development of' y7 e( j  d" T, Z/ s
individualized medicine. DNA sequence alterations and the expression profiles, L3 d7 r6 k! S7 K% m% }
of mRNA molecules and proteins can be used to predict drug response. These. i4 U$ i8 t- c, j2 X8 m
genetic and epigenetic changes may be used in turn to develop treatment# w7 G2 E& h% i/ T$ H4 i& r+ o
algorithms adjusted for use in individual patients. Several examples of such
individualized treatment, aimed at increasing drug efficacy as well as
decreasing toxicity, are discussed in this edition.1 A- }( [7 K" M5 |. ^6 O' N8 L$ [
In systemic autoimmune diseases, current clinical practice calls for
immunosuppressive drug therapy. However, some drugs are not target-specific
and some carry a high risk of side effects. New immunosuppressive strategies,
such as monoclonal antibodies and receptor antagonists, are now emerging as& c* a4 F" j! {8 I5 t" J8 [' S
potentially valuable discriminating agents for use in innovative combinations.
Such novel opportunities for therapeutic targeting in systemic autoimmune9 H) v( u0 f' B0 ]5 O- D
diseases are described in Volume 2.: X/ W6 j5 [# i! f& I
MicroRNAs (miRNAs) are a family of short noncoding regulatory RNA
molecules expressed in a variety of different cell types. These tiny RNAs have
been shown to play important biological functions and may regulate the
expression of more than 30% of human genes. Presently, evidence is emerging
that particular miRNAs may play a role in human cancer pathogenesis. Thus,
the identification of miRNA expression signatures in patients with cancer may8 x) Q) G# @2 V! s
help to identify subjects who are at high risk of developing cancer or those who' V/ I8 X1 s4 [5 I
have an early stage of cancer. In order to interfere with miRNA expression,
modified antisense oligonucleotides targeting individual miRNAs have been& N: ]7 o9 v4 i) i
developed and these agents have the potential to eventually progress into a" x8 Q9 f0 N6 X% N: |) K2 G9 K1 n
new class of therapeutic agents.
Volume II, Emerging Molecular Drug Targets and Treatment Options, was, k/ Q% C4 g6 f2 Q1 c* h
written by leading experts in the field and presents a unique source of current5 `- F3 N, q8 |- T
information. Along with Volume I, Emerging Strategies in Drug Targets and  s4 S; j, _! T' R- {1 J  j
Biomarker Discovery, this work will be of interest to researchers, pharmaceutical
companies, clinicians, and students of biology, medicine, or pharmacy.. L+ Y; s; @0 j$ P, g2 W
I would like to thank the authors for their contributions, Anne Dybwad for) K: S" b  \. H- X6 Y
critical reading of the manuscripts, and all those involved in the production of
the book.6 q' k! T: n) p) n2 I( K; Z6 z
Mouldy Sioud

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