• What is PTEN?
  • PTEN in Colorectal Cancer
  • Clinical Trials


PTEN (phosphatase and tensin homolog deleted on chromosome ten) is a lipid/protein phosphatase that plays a role in multiple cell processes, including growth, proliferation, survival, and maintenance of genomic integrity. PTEN acts as a tumor suppressor by negatively regulating the PI3K/AKT signaling pathway (Figure 1) via dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the cell membrane.

Cancer-associated alterations in PTEN often result in PTEN inactivation and thus increased activity of the PI3K-AKT pathway. Somatic mutations of PTEN occur in multiple malignancies, including gliomas, melanoma, prostate, endometrial, breast, ovarian, renal, and lung cancers. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome (for reviews see Chalhoub and Baker 2009 and Maehama 2007). PTEN activity can also be lost through other mechanisms such as epigenetic changes or post-translational modifications (Leslie and Foti 2010). Immunochemistry is often used to detect changes in expression of PTEN in tumor tissues; low expression is thought to indicate loss of PTEN expression, which would result in increased activity of the PI3K-AKT pathway.


Figure 1.
Schematic of the MAPK and PI3K pathways. Growth factor binding to receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK) and the PI3K pathway (PI3K-AKT-mTOR). The letter "K" within the schema denotes the tyrosine kinase domain.

Related Pathways

Contributors: Christine M. Lovly, M.D., Ph.D., Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. PTEN. My Cancer Genome https://www.padiracinnovation.org/content/disease/colorectal-cancer/pten/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

PTEN in Colorectal Cancer

PTEN mutations occur in 5–14% of colorectal cancers (Berg et al. 2010; COSMIC; De Roock et al. 2011; Dicuonzo et al. 2001). PTEN is a tumor suppressor gene, and loss of PTEN results in upregulation of the PI3K/ AKT pathway (Salmena et al., Cell 2008;133(3):403-414). PTEN loss of expression is observed with KRAS, BRAF, and PIK3CA mutations (De Roock et al. 2011; Laurent-Puig et al. 2009; Sartore-Bianchi et al. 2009).

Germline mutations in PTEN result in PTEN hamartoma tumor syndrome and are associated with increased risk for melanoma, breast, thyroid, endometrial, colorectal, and kidney cancer (Tan et al. 2012). George and Kopetz (2011) report that somatic PTEN mutations are weakly prognostic in stage 4 CRC patients. Research into the prognostic and predictive significance of PTEN mutations and other mechanisms for loss of PTEN expression is ongoing.

The role of PTEN loss in response to PI3K and mTOR inhibitors is being explored in clinical trials (De Roock et al. 2011; Markman et al. 2010). Preclinical studies have shown that p110α-specific PI3K inhibitors may be needed for treatment of PTEN-deficient cancers and that pan-PI3K inhibitors such as PX-866 may be effective in PIK3CA-mutated cancers and cancers showing PTEN loss (Courtney, Corcoran, and Engelman 2010). Likewise, in vitro studies have shown that inactivating mutations in the PTEN gene may confer sensitivity to PI3K-mTOR inhibitors [for review, see Courtney, Corcoran, and Engelman 2010) as well as FRAP/mTOR inhibitors (Neshat et al. 2001).

In retrospective studies, PTEN loss is associated with decreased sensitivity of colorectal cancer tumors to anti-EGFR antibodies (De Roock et al., 2011). PTEN loss is associated with lack of benefit of the anti-EGFR antibody, cetuximab (De Roock et al. 2011; Frattini et al. 2007; Laurent-Puig et al. 2009; Loupakis et al. 2009; Sartore-Bianchi et al. 2009).​

Contributors: Emily Chan, M.D., Ph.D.

Suggested Citation: Chan, E. 2015. PTEN in Colorectal Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/colorectal-cancer/pten/ (Updated June 18).

Last Updated: June 18, 2015

My Cancer Genome has released its new and improved cancer clinical trials search tool on our beta website. Please visit beta.padiracinnovation.org to check it out!

Disclaimer: The information presented at padiracinnovation.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.