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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
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Decrypting a path based approach for identifying the interplay between PI3K and GSK3 signaling cascade from the

Abhijit Das1, Barshana Bhattacharya1, Souvik Roy1

  • 1Department of Pharmacology, NSHM Knowledge Campus, Kolkata- Group of Institutions, Kolkata 700053, India.

Genes & Diseases
|June 10, 2022
PubMed

Insights

This review explores the critical roles of Glycogen Synthase Kinase 3 (GSK3) and Phosphoinositide 3-Kinase (PI3K) signaling pathways in cancer. Understanding their crosstalk offers new strategies for overcoming drug resistance and improving cancer treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer remains a leading global cause of mortality, necessitating novel therapeutic strategies.
  • Aberrantly regulated signaling pathways are crucial drivers of cancer proliferation and metastasis.
  • Glycogen Synthase Kinase 3 (GSK3) and Phosphoinositide 3-Kinase (PI3K) signaling cascades are implicated in various cancers.

Purpose of the Study:

  • To review the role of GSK3 and PI3K signaling in cancer development.
  • To elucidate the intricate crosstalk between GSK3 and PI3K signaling pathways.
  • To explore the potential of targeting GSK3 and PI3K in combination for enhanced cancer therapy.

Main Methods:

  • Literature review of studies investigating GSK3 and PI3K signaling in cancer.
  • Analysis of molecular mechanisms underlying the crosstalk between GSK3 and PI3K.
  • Evaluation of preclinical data on combined inhibition of GSK3 and PI3K.

Main Results:

  • GSK3 and PI3K signaling pathways exhibit complex interactions, including cross-activation, cross-inhibition, and pathway convergence.
  • GSK3 activity influences the efficacy of PI3K inhibitors in preclinical cancer models.
  • Combined inhibition strategies show promise in overcoming drug resistance and reducing cancer cell proliferation and metastasis.

Conclusions:

  • The crosstalk between GSK3 and PI3K signaling is a significant factor in cancer progression.
  • Targeting GSK3 in combination with PI3K inhibitors may represent a more effective therapeutic strategy.
  • Further clinical investigation is warranted to validate combination therapies involving GSK3 and PI3K inhibitors for improved cancer treatment.
Keywords:
CancerChemotherapyDrug resistanceGSK3PI3K

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