Next Article in Journal
Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases—Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept
Previous Article in Journal
Role of Notch Signaling Pathway in Glioblastoma Pathogenesis
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessPerspective
Cancers 2019, 11(3), 293; https://doi.org/10.3390/cancers11030293

Quantitative Measurement of Functional Activity of the PI3K Signaling Pathway in Cancer

Precision Diagnostics, Philips Research, High Tech Campus, 5656AE Eindhoven, The Netherlands
Received: 16 January 2019 / Revised: 14 February 2019 / Accepted: 14 February 2019 / Published: 1 March 2019
Full-Text   |   PDF [618 KB, uploaded 1 March 2019]   |  
  |   Review Reports

Abstract

The phosphoinositide 3-kinase (PI3K) growth factor signaling pathway plays an important role in embryonic development and in many physiological processes, for example the generation of an immune response. The pathway is frequently activated in cancer, driving cell division and influencing the activity of other signaling pathways, such as the MAPK, JAK-STAT and TGFβ pathways, to enhance tumor growth, metastasis, and therapy resistance. Drugs that inhibit the pathway at various locations, e.g., receptor tyrosine kinase (RTK), PI3K, AKT and mTOR inhibitors, are clinically available. To predict drug response versus resistance, tests that measure PI3K pathway activity in a patient sample, preferably in combination with measuring the activity of other signaling pathways to identify potential resistance pathways, are needed. However, tests for signaling pathway activity are lacking, hampering optimal clinical application of these drugs. We recently reported the development and biological validation of a test that provides a quantitative PI3K pathway activity score for individual cell and tissue samples across cancer types, based on measuring Forkhead Box O (FOXO) transcription factor target gene mRNA levels in combination with a Bayesian computational interpretation model. A similar approach has been used to develop tests for other signaling pathways (e.g., estrogen and androgen receptor, Hedgehog, TGFβ, Wnt and NFκB pathways). The potential utility of the test is discussed, e.g., to predict response and resistance to targeted drugs, immunotherapy, radiation and chemotherapy, as well as (pre-) clinical research and drug development. View Full-Text
Keywords: signal transduction pathway; PI3K; FOXO; assay; Bayesian model; mRNA; target gene; oxidative stress; crosstalk; cancer; immune response signal transduction pathway; PI3K; FOXO; assay; Bayesian model; mRNA; target gene; oxidative stress; crosstalk; cancer; immune response
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

van de Stolpe, A. Quantitative Measurement of Functional Activity of the PI3K Signaling Pathway in Cancer. Cancers 2019, 11, 293.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top