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Using drug response data to identify molecular effectors, and molecular “omic” data to identify candidate drugs in cancer

Abstract

The current convergence of molecular and pharmacological data provides unprecedented opportunities to gain insights into the relationships between the two types of data. Multiple forms of large-scale molecular data, including but not limited to gene and microRNA transcript expression, DNA somatic and germline variations from next-generation DNA and RNA sequencing, and DNA copy number from array comparative genomic hybridization are all potentially informative when one attempts to recognize the panoply of potentially influential events both for cancer progression and therapeutic outcome. Concurrently, there has also been a substantial expansion of the pharmacological data being accrued in a systematic fashion. For cancer cell lines, the National Cancer Institute cell line panel (NCI-60), the Cancer Cell Line Encyclopedia (CCLE), and the collaborative Genomics of Drug Sensitivity in Cancer (GDSC) databases all provide subsets of these forms of data. For the patient-derived data, The Cancer Genome Atlas (TCGA) provides analogous forms of genomic information along with treatment histories. Integration of these data in turn relies on the fields of statistics and statistical learning. Multiple algorithmic approaches may be chosen, depending on the data being considered, and the nature of the question being asked. Combining these algorithms with prior biological knowledge, the results of molecular biological studies, and the consideration of genes as pathways or functional groups provides both the challenge and the potential of the field. The ultimate goal is to provide a paradigm shift in the way that drugs are selected to provide a more targeted and efficacious outcome for the patient.

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Notes

  1. 1.

    http://www.1000genomes.org/

  2. 2.

    http://evs.gs.washington.edu/EVS/.

  3. 3.

    http://www.ncbi.nlm.nih.gov/projects/SNP/.

  4. 4.

    http://www.sanger.ac.uk/genetics/CGP/cosmic/.

  5. 5.

    http://www.broadinstitute.org/software/cprg/?q=node/11.

  6. 6.

    http://www.cancerrxgene.org.

  7. 7.

    http://dtp.nci.nih.gov/.

  8. 8.

    http://discover.nci.nih.gov/cellminer/.

  9. 9.

    http://cancergenome.nih.gov and https://tcga-data.nci.nih.gov/tcga/.

  10. 10.

    http://discover.nci.nih.gov/gominer/index.jsp.

  11. 11.

    http://www.broadinstitute.org/gsea/index.jsp.

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Acknowledgments

Our studies are supported by the Center for Cancer Research, Intramural Program of the National Cancer Institute (Z01 BC 006150). This work was also supported in part by a MSKCC Genome Data Analysis Center Grant (U24 CA143840) awarded as part of the National Cancer Institute (NCI)/National Human Genome Research Institute (NHGRI).

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Correspondence to William C. Reinhold or Yves G. Pommier.

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Reinhold, W.C., Varma, S., Rajapakse, V.N. et al. Using drug response data to identify molecular effectors, and molecular “omic” data to identify candidate drugs in cancer. Hum Genet 134, 3–11 (2015). https://doi.org/10.1007/s00439-014-1482-9

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Keywords

  • Vemurafenib
  • Cell Line Panel
  • Prior Biological Knowledge
  • Developmental Therapeutics Program
  • Cancer Cell Line Encyclopedia