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Cell signaling and cancer: a mechanistic insight into drug resistance

Munmun Panda1, Bijesh K Biswal2

  • 1Cancer Drug Resistance Laboratory, Department of Life Science, National Institute of Technology, Sundargarh, Rourkela, Odisha, 769008, India.

Molecular Biology Reports
|July 8, 2019
PubMed

Insights

Drug resistance in cancer hinders treatment effectiveness. This review details resistance mechanisms and signaling pathways, proposing combination therapies for improved cancer treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Drug resistance is a significant challenge in cancer therapeutics, impacting treatment efficacy.
  • The increasing prevalence of drug resistance necessitates novel therapeutic approaches targeting cancer cells genetically.

Purpose of the Study:

  • To review mechanisms of cancer drug resistance.
  • To explore the role of signaling pathways in drug resistance.
  • To summarize contemporary strategies for overcoming drug resistance.

Main Methods:

  • Literature review of mechanisms contributing to drug resistance.
  • Analysis of signaling pathways implicated in cancer drug resistance.
  • Synthesis of evidence on combination therapies for cancer treatment.

Main Results:

  • Identified multiple resistance mechanisms: drug efflux, target alteration, alternative splicing, extracellular vesicles, tumor heterogeneity, epithelial-mesenchymal transition, tumor microenvironment, secondary mutations, epigenetic alterations, receptor heterodimerization, and target amplification.
  • Detailed the involvement of EGFR, Ras, PI3K/Akt, Wnt, Notch, TGF-β, and Integrin-ECM signaling pathways in drug resistance.
  • Highlighted combination therapy involving specific signaling pathway inhibitors and cancer drugs as a promising strategy.

Conclusions:

  • Understanding diverse drug resistance mechanisms is crucial for developing effective cancer treatments.
  • Targeting specific signaling pathways in combination with conventional drugs offers a promising avenue for overcoming resistance.
  • Novel therapeutic strategies are essential to improve outcomes for cancer patients facing drug resistance.
Keywords:
Aberrant signalingCancerCross-resistanceDrug resistanceTherapeutics

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