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Updated: Oct 20, 2025

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Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance

Christiana M Neophytou1,2, Ioannis P Trougakos3,4, Nuray Erin5

  • 1European University Research Center, Nicosia 2404, Cyprus.

Cancers
|September 10, 2021
PubMed

Insights

Cancer cells evade apoptosis, leading to multi-drug resistance (MDR). This review explores how altered apoptosis pathways and the tumor microenvironment drive MDR, and discusses therapeutic strategies targeting these mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor cells' evasion of apoptosis is a hallmark of cancer, contributing to multi-drug resistance (MDR).
  • Deregulation of apoptotic pathways, including the Bcl-2 superfamily, Inhibitors of Apoptosis (IAP) proteins, and tumor suppressor p53, is implicated in MDR.
  • The PI3K/AKT pathway and tumor microenvironment factors also play critical roles in promoting cancer cell survival and resistance.

Purpose of the Study:

  • To review alterations in apoptosis and related pathways that promote MDR.
  • To summarize current and emerging therapeutic strategies for overcoming MDR.
  • To highlight the potential of epigenetic modifications in reversing MDR.

Main Methods:

  • Literature review of studies on apoptosis, MDR, and therapeutic interventions.
  • Analysis of molecular mechanisms underlying apoptosis evasion and drug resistance.
  • Synthesis of information on targeted therapies and natural compounds.

Main Results:

  • Key alterations in apoptosis pathways (Bcl-2, IAPs, p53) and the PI3K/AKT pathway contribute to MDR.
  • The tumor microenvironment can actively inhibit apoptosis and reduce drug efficacy.
  • Various therapeutic approaches, including targeted agents and natural compounds, show promise against resistant tumors.

Conclusions:

  • Understanding the interplay between apoptosis evasion and MDR is crucial for developing effective cancer treatments.
  • Targeting specific molecular pathways and exploiting the tumor microenvironment offer potential strategies to overcome resistance.
  • Epigenetic modifications represent a promising avenue for reversing the MDR phenotype and improving patient outcomes.
Keywords:
Bcl-2 family of proteinsPI3K/AKT pathwayapoptosiscancer associated fibroblastscancer therapycaspase-dependent deathepigenetic modificationsmulti-drug resistancetumor-microenvironment

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