Related Experiment Video

Updated: May 3, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

6.5K

Assessing PIK3CA and PTEN in early-phase trials with PI3K/AKT/mTOR inhibitors

Filip Janku1, David S Hong1, Siqing Fu1

  • 1Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Cell Reports
|January 21, 2014
PubMed

Insights

Genetic aberrations in PIK3CA and PTEN are common in advanced cancers. Targeting the PI3K/AKT/mTOR pathway with inhibitors showed clinical actionability, especially for specific PIK3CA mutations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Preclinical studies suggest PIK3CA and PTEN gene aberrations are important in cancer.
  • Clinical actionability of these aberrations remains unclear in advanced, refractory cancers.

Purpose of the Study:

  • To investigate the clinical actionability of PIK3CA and PTEN gene aberrations.
  • To identify predictive biomarkers for treatment response in advanced cancers.

Main Methods:

  • Genomic profiling of 1,656 patients with advanced, refractory cancers.
  • Analysis of PIK3CA mutations and PTEN loss/mutation.
  • Multivariable analysis to identify factors predicting response to phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) inhibitors.

Main Results:

  • PIK3CA mutations detected in 9% and PTEN aberrations in 13% of patients.
  • Treatment with PI3K/AKT/mTOR inhibitors was the sole independent predictor of response in patients with PIK3CA or PTEN aberrations.
  • A subgroup with H1047R PIK3CA mutations achieved 45% rate of stable disease or partial response.

Conclusions:

  • Aberrations in the PI3K/AKT/mTOR pathway are prevalent and clinically actionable in advanced cancers.
  • Biomarker-driven clinical trials incorporating rational drug combinations are validated for accelerated use.

More Related Videos

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

5.7K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

19.0K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.5K