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Published on: August 23, 2024
The PI3K Pathway in Human Disease
David A Fruman1, Honyin Chiu1, Benjamin D Hopkins2
1Department of Molecular Biology & Biochemistry, University of California, Irvine, Irvine, CA 92697-3900, USA.
Abstract:
Phosphoinositide 3-kinase (PI3K) activity is stimulated by diverse oncogenes and growth factor receptors, and elevated PI3K signaling is considered a hallmark of cancer. Many PI3K pathway-targeted therapies have been tested in oncology trials, resulting in regulatory approval of one isoform-selective inhibitor (idelalisib) for treatment of certain blood cancers and a variety of other agents at different stages of development. In parallel to PI3K research by cancer biologists, investigations in other fields have uncovered exciting and often unpredicted roles for PI3K catalytic and regulatory subunits in normal cell function and in disease. Many of these functions impinge upon oncology by influencing the efficacy and toxicity of PI3K-targeted therapies. Here we provide a perspective on the roles of class I PI3Ks in the regulation of cellular metabolism and in immune system functions, two topics closely intertwined with cancer biology. We also discuss recent progress developing PI3K-targeted therapies for treatment of cancer and other diseases.
Insights
Phosphoinositide 3-kinase (PI3K) signaling is crucial in cancer. New research explores PI3K
Area of Science:
- Oncology and Molecular Biology
Background:
- Elevated phosphoinositide 3-kinase (PI3K) signaling is a hallmark of cancer, driven by oncogenes and growth factors.
- PI3K pathway-targeted therapies are advancing, with some approved for blood cancers and others in development.
Purpose of the Study:
- To provide a perspective on the roles of class I PI3Ks in cellular metabolism and immune function.
- To discuss how these roles impact PI3K-targeted cancer therapies.
- To review recent progress in developing PI3K-targeted therapies for cancer and other diseases.
Main Methods:
- Review of existing literature and research findings on PI3K functions.
- Analysis of the interplay between PI3K, metabolism, immunity, and cancer.
- Discussion of current and emerging PI3K-targeted therapeutic strategies.
Main Results:
- PI3K subunits play significant roles in normal cellular metabolism and immune system functions.
- These non-oncogenic roles can influence the efficacy and toxicity of PI3K-targeted cancer therapies.
- Diverse PI3K inhibitors are in various stages of clinical development for multiple diseases.
Conclusions:
- Understanding the broader functions of PI3Ks in metabolism and immunity is critical for optimizing cancer therapy.
- Further research into PI3K regulation and targeted inhibition holds promise for improved cancer treatment and management of related toxicities.
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