The dark side of the moon: The PI3K/PTEN/AKT pathway in colorectal carcinoma

Nicola Silvestris, Stefania Tommasi, Daniela Petriella, Daniele Santini, Ettore Fistola, Antonio Russo, Gianmauro Numico, Giuseppe Tonini, Evaristo Maiello, Giuseppe Colucci

Research output: Contribution to journalArticlepeer-review


Wild-type KRAS status is required but not sufficient to confer sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in colorectal cancer patients. As a consequence, one of the major challenges is to identify, in non-mutant KRAS patients, other markers that can predict lack of response to this therapy. Small series have investigated the clinical effect of PIK3CA mutations on resistance to anti-EGFR mAbs and discrepant results have been observed. Furthermore, PTEN loss in metastases may be predictive of resistance to anti-EGFR mAbs, even if PTEN determination is far from an immediate clinical application. The introduction of modulators of the PI3K/AKT/mTOR pathway as potential targeted anticancer drugs is encouraging, but this attractive therapy option is still at an early stage of development.

Original languageEnglish
Pages (from-to)69-74
Number of pages6
Issue numberSUPPL. 1
Publication statusPublished - Feb 2010


  • AKT
  • Cetuximab
  • MTOR
  • Panitumumab
  • Phosphoinositide 3-kinases
  • PTEN

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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