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Toxicology and Applied Pha

Editorial

Molecular biomarkers: Challenges and prospects for the future

Various modern molecular and cellular approaches to

assessing the toxicity of inorganic or organic chemicals either

alone or as mixtures are described in this special issue of

Toxicology and Applied Pharmacology. These evolving

techniques have great potential for use in guiding societal

decisions about chemical agents. In particular, the bomicQ(genomic, proteomic, metabolomic/metabonomic) bio-

markers must be rigorously evaluated both in terms of their

ability to predict time course/dose–response relationships and

in terms of identifyingmeaningful changes in thesemolecular

systems that predict long-term health outcomes. There is

hence a pressing need for the translation of these tools from

basic science for use in both risk assessment and clinical

practice. These matters are not trivial in import to society or

depth of the translational research that will be required to

incorporate molecular biomarkers into common use. For this

to happen, several major challenges must be addressed.

About 80,000 to 100,000 chemicals are in commercial use

in the United States. Of these, the toxic properties of perhaps

500 to 1000 are truly understood in any detail or depth.

Further, about 1000 new chemicals are added each year.

Public health professionals and the toxicological community,

in particular, are under great pressure to evaluate a large

number of commonly used chemicals, as well as drugs, in a

more timely manner. The application of modern analytical

technologies for assessing chemical exposures coupled with

molecular/cellular tools for evaluating early or low-dose

biological responses at the target cell level should permit

great advances in delineating the btarget doseQ of chemical

agents or drugs for sensitive cell populations. These

technologies linked to rapid information processing could

greatly accelerate the speed with which chemicals or drugs

are evaluated. The incorporation of robotic technology

should also serve to increase the speed of these assessments

by increasing throughput. All of these advances are now

occurring. Important societal goals for ensuring the safety of

chemicals and drugs are clearly achievable if the appropriate

resources continue to be applied.

A second, and undoubtedly greater challenge, involves

the validation and interpretation of molecular biomarker

data. This critical component may prove to be difficult and

time consuming. For molecular biomarkers to become

accepted and reach their full potential as instruments for

0041-008X/$ - see front matter D 2005 Published by Elsevier Inc.

doi:10.1016/j.taap.2005.05.013

societal decision making or clinical use, validation studies

that permit interpretation of the health consequences of

chemical/drug exposure assessment data and molecular

biomarker responses must be conducted in a variety of test

systems. This achievement is essential if molecular bio-

markers are to play a meaningful role in bscience-baseddecision making.Q Because data generated by these

approaches are quantifiable, they lend themselves to rigorous

statistical analysis. The incorporation of biomarkers into

clinical trials or molecular epidemiology studies will add a

new dimension of objective information for making safety

assessment decisions about drugs or chemicals either alone

or in mixture combinations. This challenge is enormous and

calls for new interdisciplinary coordination of efforts. It is

achievable if government, academe, and industry work

together to address the overarching issue of data interpreta-

tion. If this cooperation does not occur, the question of how

to interpret exposure assessment or molecular biomarker

data and what these data actually signify will continue to be a

matter of opinion. For example, the need for differentiation

of chemical-specific changes in these molecular systems that

represent a bcellular sneezeQ of no particular health con-

sequence from those changes that are harbingers of

deleterious health outcomes such as cancer, kidney failure,

or Alzheimer’s disease cannot be overemphasized. Once

fully validated, the molecular biomarker approaches

described in this special issue of Toxicology and Applied

Pharmacology may clearly prove very useful in the early

detection or even prevention of such diseases. This challenge

can be addressed only through a focused and concerted

effort. The promise of new, faster, and readily interpretable

molecular diagnostic tools that can serve to prevent or help

interdict a host of devastating diseases makes the investment

of time, energy, and resources worth the effort.

In summary, the future of molecular biomarkers holds

both great challenges and great promise. Continuing the

development and validation of molecular biomarkers is

clearly linked to the improvement of the health of future

generations. The scientific journey in this area promises to be

exciting and the achievements can be great if the principles of

sound science are adhered to in a diligent manner.

Bruce A. Fowler

rmacology 206 (2005) 97