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Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced

Pallab Shaw1, Arpan Dey Bhowmik2, Mohan Shankar Gopinatha Pillai2

  • 1Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences, Oklahoma City, 73104, Oklahoma, USA; Department of Pathology, The University of Oklahoma Health Sciences, Oklahoma City, 73104, Oklahoma, USA.

Cancer Letters
|April 28, 2025
PubMed

Insights

Anoikis resistance (AR) allows cancer cells to spread. This review details AR mechanisms, epigenetic regulation, and therapeutic targets to combat cancer metastasis.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Anoikis is programmed cell death upon loss of cell-extracellular matrix (ECM) and cell-cell interactions, vital for tissue homeostasis.
  • Cancer cells develop anoikis resistance (AR), a key factor enabling metastasis.
  • AR involves complex alterations in apoptotic signaling, metabolism, autophagy, and epigenetics.

Purpose of the Study:

  • To review the mechanisms of anoikis and anoikis resistance (AR) in cancer.
  • To discuss recent findings on epigenetic regulation of AR and its role in metastasis (2014-2024).
  • To highlight therapeutic strategies and potential protein targets for combating AR and cancer metastasis.

Main Methods:

  • Comprehensive review of literature on anoikis and anoikis resistance.
  • Focus on intrinsic and extrinsic apoptotic pathways, cell-ECM interactions, and autophagy.
  • Network analysis of 122 AR-associated proteins to identify potential therapeutic targets.

Main Results:

  • Anoikis resistance is driven by disruptions in cell survival pathways, metabolic adaptations, and epigenetic modifications.
  • Epigenetic regulation plays a significant role in promoting AR and facilitating cancer cell metastasis.
  • Network analysis identified 53 hub proteins as potential therapeutic targets for AR.

Conclusions:

  • Understanding anoikis resistance mechanisms is critical for developing effective anti-metastasis therapies.
  • Targeting AR, particularly through identified hub proteins and epigenetic modulators, holds promise for cancer treatment.
  • Further research using advanced in vitro and in vivo models is essential to validate therapeutic strategies against cancer metastasis.
Keywords:
Anoikis resistanceApoptosisCancerMetastasisNetwork analysis

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