Genome sequencing identifies a basis for everolimus sensitivity Academic Article uri icon


MeSH Major

  • Antineoplastic Agents
  • Drug Resistance, Neoplasm
  • Sirolimus
  • Tumor Suppressor Proteins
  • Urinary Bladder Neoplasms


  • Cancer drugs often induce dramatic responses in a small minority of patients. We used whole-genome sequencing to investigate the genetic basis of a durable remission of metastatic bladder cancer in a patient treated with everolimus, a drug that inhibits the mTOR (mammalian target of rapamycin) signaling pathway. Among the somatic mutations was a loss-of-function mutation in TSC1 (tuberous sclerosis complex 1), a regulator of mTOR pathway activation. Targeted sequencing revealed TSC1 mutations in about 8% of 109 additional bladder cancers examined, and TSC1 mutation correlated with everolimus sensitivity. These results demonstrate the feasibility of using whole-genome sequencing in the clinical setting to identify previously occult biomarkers of drug sensitivity that can aid in the identification of patients most likely to respond to targeted anticancer drugs.

publication date

  • October 12, 2012



  • Academic Article



  • eng

PubMed Central ID

  • PMC3633467

Digital Object Identifier (DOI)

  • 10.1126/science.1226344

PubMed ID

  • 22923433

Additional Document Info

start page

  • 221


  • 338


  • 6104