Emerging Opportunities for Target Discovery in Rare Cancers

Cell Chem Biol. 2017 Sep 21;24(9):1075-1091. doi: 10.1016/j.chembiol.2017.08.002.


Rare cancers pose unique challenges to research due to their low incidence. Barriers include a scarcity of tissue and experimental models to enable basic research and insufficient patient accrual for clinical studies. Consequently, an understanding of the genetic and cellular features of many rare cancer types and their associated vulnerabilities has been lacking. However, new opportunities are emerging to facilitate discovery of therapeutic targets in rare cancers. Online platforms are allowing patients with rare cancers to organize on an unprecedented scale, tumor genome sequencing is now routinely performed in research and clinical settings, and the efficiency of patient-derived model generation has improved. New CRISPR/Cas9 and small-molecule libraries permit cancer dependency discovery in a rapid and systematic fashion. In parallel, large-scale studies of common cancers now provide reference datasets to help interpret rare cancer profiling data. Together, these advances motivate consideration of new research frameworks to accelerate rare cancer target discovery.

Keywords: CRISPR/Cas9; chordoma; conditionally reprogrammed cells; genomics; next-generation sequencing; organoid; patient-derived xenograft; rare cancer; small-molecule screen; target discovery.

Publication types

  • Review

MeSH terms

  • CRISPR-Cas Systems
  • Drug Discovery*
  • Humans
  • Imatinib Mesylate / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Precision Medicine
  • RNA Interference
  • Small Molecule Libraries / chemistry


  • Small Molecule Libraries
  • Imatinib Mesylate