2. Academic Validation
  3. PI3K inhibitors are finally coming of age

PI3K inhibitors are finally coming of age

  • Nat Rev Drug Discov. 2021 Oct;20(10):741-769. doi: 10.1038/s41573-021-00209-1.
Bart Vanhaesebroeck 1,  Matthew W D Perry 2,  Jennifer R Brown 3,  Fabrice André 4,  Klaus Okkenhaug 5
Affiliations

Affiliations

  • 1 UCL Cancer Institute, University College London, London, UK. [email protected].
  • 2 Medicinal Chemistry, Research and Early Development, Respiratory & Immunology BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • 3 CLL Center, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • 4 Institut Gustave Roussy, INSERM U981, Université Paris Saclay, Paris, France.
  • 5 Department of Pathology, University of Cambridge, Cambridge, UK.
PMID: 34127844 DOI: 10.1038/s41573-021-00209-1
Abstract

Overactive phosphoinositide 3-kinase (PI3K) in Cancer and immune dysregulation has spurred extensive efforts to develop therapeutic PI3K inhibitors. Although progress has been hampered by issues such as poor drug tolerance and drug resistance, several PI3K inhibitors have now received regulatory approval - the PI3Kα isoform-selective inhibitor alpelisib for the treatment of breast Cancer and inhibitors mainly aimed at the leukocyte-enriched PI3Kδ in B cell malignancies. In addition to targeting Cancer cell-intrinsic PI3K activity, emerging evidence highlights the potential of PI3K inhibitors in Cancer Immunotherapy. This Review summarizes key discoveries that aid the clinical translation of PI3Kα and PI3Kδ inhibitors, highlighting lessons learnt and future opportunities.

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