Oncology biomarker qualification initiative

In 2006, the US FDA, the NCI, and the Centers for Medicare

and Medicaid (CMS) created a new Oncology Biomarker

Qualification Initiative (OBQI) with the aim of using

biomarkers, including genomic and proteomic markers, to

help develop drugs and diagnostics. Specific areas of

scientific activities include the application of platform

technologies for assessing genomic and proteomic

alterations, multiplexed molecular assays and advanced

imaging modalities. As part of the alliance, the NCI seeks to

develop technologies to improve the detection, diagnosis,

treatment and prevention of cancer; the FDA is interested in

exploring biomarker technologies as assessment tools for use

in FDA guidance to facilitate cancer drug development; and

the CMS is interested in the development of evidence to

inform reimbursement decision making about existing or

new treatment regimens. The goal of OBQI is to validate

particular biomarkers so that they can be used to evaluate

new and promising technologies in a manner that will

shorten clinical trials, reduce the time and resources spent

during the drug development process, improve the linkage

between drug approval and drug coverage, and increase the

safety and appropriateness of drug choices for cancer

patients. The first OBQI project will investigate FDG-PET

imaging as a predictor of tumor response in patients with

non-Hodgkin's lymphoma. Under the agreement, the three

agencies will collaborate to develop strategic plans, set

priorities and leverage resources including the private

sector, toward the goal of improving the clinical utility of

biomarker technology. OBQI will continue to develop public

resources, including databases and obtaining laboratory

specimens, and seek input from private sector partners

through direct research or funding.

Challenges for the discovery of cancer biomarkers

A major challenge will be the integration of proteomics with

genomics and metabolomics data and their functional

interpretation in conjunction with clinical results and

epidemiology. A number of genes are up- and

downregulated in cancer, making it problematic to rely on

any single tumor biomarker even for one type of cancer. The

physiological properties of the microenvironment of a

majority (90%) of tumors, such as hypoxia, acidity, and

changes in temperature, are considered promising

environmental markers for tumor targeting. Hypoxia and

acidosis are hallmarks of tumors at both very early and

advanced stages of tumor development.

Considerable scientific effort has gone into finding common

SNPs that correlate with risk for cancer. Protein biomarkers

are now considered to be more effective in risk assessment,

early detection, and cancer prevention. However,

proteomics researchers have not discovered sufficient

cancer-related biomarkers and this is where the bottleneck

lies. There is a need for accelerating research efforts if

protein biomarker identification and validation are to have

an impact in battling the disease. Multiplexing could make

trials much more high-throughput and accelerate protein

biomarker discovery. There is a need for efficient, low-cost

assays to develop and validate candidate biomarkers.

Conclusions

Cancer biomarkers play an important role in understanding

the pathobiological mechanism of cancer as well as

providing targets for drug discovery. Several technologies

have been applied for discovery of biomarkers of cancer.

Proteomics is important but has been an under-exploited

technology. Among the various types of cancer biomarkers,

methylated DNA sequences, mitochondrial DNA and

miRNA expression profiling are assuming increasing

importance. Although numerous biomarkers of various

types of cancer have been discovered, few have been

validated and there is a need for more exact molecular

biomarkers for use in clinical trials and in oncology practice.

The development of personalized medicine is closely linked

to biomarkers, which may serve as the basis for diagnosis,

drug discovery and monitoring of diseases.