The Phosphoinositide-3-Kinase-Akt-mTOR Pathway as a Therapeutic Target in Breast Cancer

The phosphoinositide-3-kinase (PI3-kinase)-Akt-mTOR pathway is a central signal transduction pathway that regulates many critical aspects of normal and cancer physiology, including cell proliferation, apoptosis, cell morphology and migration, protein synthesis, and integration of metabolism. In breast cancer, somatic mutations that activate the pathway occur in more than 50% of tumors, underscoring the potentially broad impact of targeting the pathway for therapy. A vast body of preclinical data demonstrates the efficacy of pathway inhibition on tumor growth, and evidence also shows that activation of the pathway occurs in models of acquired resistance to hormonal therapy. This preclinical work led to the investigation of allosteric mTOR inhibitors, everolimus and temsirolimus, in metastatic hormone receptor–positive breast cancer. The recent BOLERO-2 trial comparing everolimus plus exemestane versus placebo plus exemestane in women with resistance to nonsteroidal aromatase inhibitors demonstrated a 6-month improvement in progression-free survival and led to FDA approval of everolimus for this indication in the United States. This landmark trial is the first demonstration of significant clinical benefit using drugs targeting this pathway in breast cancer. Many questions remain about the role of everolimus and other pathway-targeting drugs in clinical development in breast cancer treatment. This article reviews the role of the PI3-kinase-Akt-mTOR pathway in breast cancer biology and the clinical trial evidence available to date.

Target Audience

This activity has been designated to meet the educational needs of physicians and nurses involved in the management of patients with cancer.

Learning Objectives

Upon completion of this activity, participants will be able to:

  • Describe the role of the PI3-kinase-Akt-mTOR pathway in breast cancer treatment
  • Outline the recent clinical trials for pathway-targeting drugs for the treatment of breast cancer
Additional information
Supporters: 

No commercial support was received for this article.

Course summary
Available credit: 
  • 1.00 Participation
  • 1.00 Nurse
  • 1.00 Physician
Course opens: 
06/10/2013
Course expires: 
06/10/2014
Cost:
$0.00

Josh Lauring MD, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland


Ben Ho Park, MD, PhD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland


Antonio C. Wolff, MD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland

Available Credit

  • 1.00 Participation
  • 1.00 Nurse
  • 1.00 Physician

Accreditation Period

Course opens: 
06/10/2013
Course expires: 
06/10/2014

Price

Cost:
$0.00
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Required Hardware/software

To access this activity, users will need:

  • A device with an Internet connection
  • Adobe Reader or other PDF reader software for article and certificate viewing/printing