Towards patient-based cancer therapeutics

Abstract

A new approach to the discovery of cancer therapeutics is emerging that begins with the cancer patient. Genomic analysis of primary tumors is providing an unprecedented molecular characterization of the disease. The next step requires relating the genetic features of cancers to acquired gene and pathway dependencies and identifying small-molecule therapeutics that target them.

Figure 1

The Cancer Target Discovery and Development (CTD²) Network of the NCI aims to relate the genetic features of cancers to acquired cancer dependencies and to identify small molecules that target the dependencies (superscript numbers refer to: ¹Broad Institute of Harvard and MIT; ²Cold Spring Harbor Laboratory; ³Columbia University; ⁴Dana Farber Cancer Institute; ⁵University of Texas Southwestern Medical Center at Dallas).

Figure 2

Conceptual image of a matrix of data relating cancer genotype, cancer phenotype and sensitivity to highly specific small-molecule modulators of cancer-relevant proteins. The CTD² Network is performing quantitative cellular measurements using small molecules (both with and without a knowledge or their targets) and genetically characterized cancer cell lines (copy number variation; mutational status; gene expression). Computational analyses are being performed that correlate the pattern of sensitivity with the genetic features of the cancer cell lines–. These analyses yield hypotheses for cancer genotype/drug efficacy relationships that can be tested in vitro and in vivo using systems developed within the Network.