Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: Promises and perils

Davide Torti, Livio Trusolino

Research output: Contribution to journalArticle

Abstract

A decade has elapsed since the concept of oncogene addiction was first proposed. It postulates that - despite the diverse array of genetic lesions typical of cancer - some tumours rely on one single dominant oncogene for growth and survival, so that inhibition of this specific oncogene is sufficient to halt the neoplastic phenotype. A large amount of evidence has proven the pervasive power of this notion, both in basic research and in therapeutic applications. However, in the face of such a considerable body of knowledge, the intimate molecular mechanisms mediating this phenomenon remain elusive. At the clinical level, successful translation of the oncogene addiction model into the rational and effective design of targeted therapeutics against individual oncoproteins still faces major obstacles, mainly due to the emergence of escape mechanisms and drug resistance. Here, we offer an overview of the relevant literature, encompassing both biological aspects and recent clinical insights. We discuss the key advantages and pitfalls of this concept and reconsider it as an illustrative principle to guide post-genomic cancer research and drug development.

Original languageEnglish
Pages (from-to)623-636
Number of pages14
JournalEMBO Molecular Medicine
Volume3
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • DNA damage
  • Drug development
  • Oncogene addiction
  • Targeted therapies
  • Tyrosine kinases

ASJC Scopus subject areas

  • Molecular Medicine

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