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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

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Targeting PI3K signaling in cancer: Challenges and advances

Maria Chiara De Santis1, Federico Gulluni1, Carlo Cosimo Campa2

  • 1Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Biochimica Et Biophysica Acta. Reviews on Cancer
|April 5, 2019
PubMed

Insights

Phosphoinositide 3-kinase (PI3K) inhibitors show promise but face challenges with side effects. New strategies and isoform-specific drugs are improving PI3K inhibitor therapies and exploring other classes.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Oncology

Background:

  • The phosphoinositide 3-kinase (PI3K) pathway is crucial in cellular functions and disease.
  • Targetable proteins within the PI3K pathway have spurred the development of small molecule inhibitors.
  • Clinical translation of PI3K inhibitors has been hindered by dose-limiting, on-target adverse effects.

Purpose of the Study:

  • To review challenges and advancements in PI3K inhibitor clinical trials.
  • To highlight the development of isoform-specific PI3K inhibitors.
  • To discuss novel strategies for mitigating PI3K inhibitor toxicity and explore class II and III PI3K inhibitors.

Main Methods:

  • Literature review of PI3K inhibitors in clinical trials.
  • Analysis of emerging therapeutic strategies for PI3K inhibition.
  • Examination of the roles of different PI3K classes.

Main Results:

  • Clinical trials of PI3K inhibitors have faced significant hurdles due to toxicity.
  • Development of isoform-specific inhibitors and new therapeutic approaches are showing promise.
  • Class II and III PI3K inhibitors are emerging, clarifying their distinct roles.

Conclusions:

  • Overcoming toxicity is key to successful PI3K inhibitor therapy.
  • Isoform specificity and novel strategies are paving the way for a new era of PI3K inhibitors.
  • Understanding the non-redundant roles of all PI3K classes is essential for comprehensive therapeutic development.
Keywords:
Combination therapyPI3KPathway inhibitorsSystemic toxicity

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