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Last Updated: 07/21/14

Director’s Challenge: Toward a Molecular Classification of Cancer


The “Director’s Challenge: Toward a Molecular Classification of Cancer” (1999-2004) challenged the cancer research community to demonstrate the power of comprehensive molecular technologies by developing profiles of molecular alterations in human tumors. These “molecular signatures” were intended to redefine tumor classification, moving from morphology-based to molecular-based classification schemes.

The Director’s Challenge investigators developed strategies for analyzing tumor specimens using technologies including:

  • cDNA and oligo microarray analysis of gene expression
  • Comparative genomic hybridization (CGH)
  • Serial analysis of gene expression (SAGE)
  • Spectral karyotyping (SKY)
  • Arbitrarily primed and quantitative–PCR
  • 2D Gel/MS analysis of protein expression
  • Analysis of patterns of DNA methylation.

Grantees sought “molecular signatures” associated with:

  • Responsiveness to therapy
  • Prognosis after curative surgery
  • Disease progression
  • Risk of metastasis
  • Inter and intra-tumor heterogeneity

The Director’s Challenge investigators in collaboration with the NCI addressed issues of the management, analysis and public release of the large, complex data sets developed on these projects.

Several “signatures” discovered in Director’s Challenge projects were further developed in the subsequent research program Strategic Partnerships to Evaluate Cancer Signatures (SPECS I).

NCI is dedicated to making the information, analytical tools, reagents and protocols developed by the Director’s Challenge Initiative and other NCI activities available to the cancer research community. NCI continues to support the development and applications of new technologies.