A framework for understanding and targeting residual disease in oncogene-driven solid cancers

Nat Med. 2016 May 5;22(5):472-8. doi: 10.1038/nm.4091.


Molecular targeted therapy has the potential to dramatically improve survival in patients with cancer. However, complete and durable responses to targeted therapy are rare in individuals with advanced-stage solid cancers. Even the most effective targeted therapies generally do not induce a complete tumor response, resulting in residual disease and tumor progression that limits patient survival. We discuss the emerging need to more fully understand the molecular basis of residual disease as a prelude to designing therapeutic strategies to minimize or eliminate residual disease so that we can move from temporary to chronic control of disease, or a cure, for patients with advanced-stage solid cancers. Ultimately, we propose a shift from the current reactive paradigm of analyzing and treating acquired drug resistance to a pre-emptive paradigm of defining the mechanisms that result in residual disease, to target and limit this disease reservoir.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Resistance, Neoplasm*
  • Humans
  • Immunotherapy / methods*
  • Molecular Targeted Therapy
  • Neoplasm, Residual / drug therapy*
  • Neoplasm, Residual / genetics
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Oncogenes / genetics