Table 1.

Oncogene addiction: studies in mice, studies in human cancer cell lines, and clinical evidence

Studies in mice *
Targeted oncogeneCancer type
c-mycT cell and acute myeloid Leukemia
Bcr-AblLeukemia
H-rasMelanoma
K-rasLung
c-mycPancreatic β-cell
c-mycOsteogenic sarcoma
Her-2/neuBreast
c-mycBreast
Wnt-1Breast
Studies in human cancer cell lines
Targeted oncogeneCancer cell line
Her-2Breast
Cyclin D1Esophagus, colon, pancreatic, squamous, nasopharyngeal
K-rasmutPancreatic
K-rasv12Pancreatic
β-CateninColon
Cyclin ELiver
Mutant β-RafMelanoma
MITFMelanoma
Clinical evidence
Targeted oncogene (s)DiseaseAgent
HER-2Breast §, Trastuzumab (combination)
BCR/ABLChronic myeloid leukemia §Imatinib (monotherapy)
C-KITGastrointestinal stromal tumor §Imatinib (monotherapy)
EGFRNSCLC §Gefitinib, erlotinib § (monotherapy)
EGFRHead and neck, colorectal §Cetuximab (combination)
EGFRPancreas §Erlotinib (combination)
VEGFBreast, colorectal §, , kidneyBevacizumab (combination)
VEGFR, RAFKidney §Sorafenib (monotherapy)
  • NOTE: For specific references and further details, see ref. 6.

  • * Switching off the indicated oncogene led to growth inhibition, differentiation, apoptosis and/or tumor regression.

  • Treatment of these cell lines with an antisense oligonucleotide or a RNAi directed to the respective oncogene caused growth inhibition, and in some cases, decreased tumorigenicity and increased chemosensitivity.

  • Treatment regimen indicates agent alone (monotherapy) or in combination with cytotoxic agents (combination).

  • § Food and Drug Administration–approved.

  • Phase III evidence shows improved disease-free or overall survival rates.