Collateral Lethality in Pancreatic Cancer

Cancer Discov. 2017 Apr;7(4):342-343. doi: 10.1158/2159-8290.CD-NB2017-019. Epub 2017 Feb 7.

Abstract

The chromosome 18q21 deletion in nearly one third of pancreatic adenocarcinomas eliminates not only the tumor suppressor SMAD4, but also neighboring genes with important cellular roles, such as ME2 This is tolerated by cancer cells only because ME2 has a functionally redundant paralog, ME3, elsewhere in the genome. A study shows that these cells are vulnerable to ME3 silencing; this concept of collateral lethality could provide a new therapeutic strategy for a difficult-to-treat disease.

MeSH terms

  • Chromosome Deletion
  • Chromosome Disorders / complications
  • Chromosome Disorders / genetics
  • Chromosome Disorders / mortality*
  • Chromosomes, Human, Pair 18 / genetics
  • Humans
  • Malate Dehydrogenase / genetics*
  • Mutation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / mortality*
  • Pancreatic Neoplasms / pathology
  • Smad4 Protein / genetics*

Substances

  • Smad4 Protein
  • Malate Dehydrogenase
  • malic enzyme 2; human

Supplementary concepts

  • Chromosome 18 deletion syndrome