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Updated: Jul 1, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
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Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

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Induction of Multiple Alternative Mitogenic Signaling Pathways Accompanies the Emergence of Drug-Tolerant Cancer

Frank V Celeste1,2, Scott Powers1,2

  • 1Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA.

Cancers
|March 13, 2024
PubMed

Insights

Cancer cells develop drug tolerance through bypass pathways. Targeting multiple alternative mitogenic pathways, not just one, is crucial for effective cancer therapy and preventing drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Systems Biology

Background:

  • Drug resistance in cancer arises from surviving cells forming drug-tolerant populations.
  • Specific bypass pathways are implicated as therapeutic targets for preventing drug tolerance.

Purpose of the Study:

  • To investigate the development of drug tolerance in EGFR-mutant lung adenocarcinoma and BRAF-mutant melanoma using a systems-biology approach.
  • To identify alternative mitogenic pathways activated during drug tolerance.

Main Methods:

  • Proteomics and genomics were employed to analyze cancer cell lines.
  • Examined drug tolerance to EGFR inhibitors in lung cancer and BRAF inhibitors in melanoma.

Main Results:

  • Multiple alternative mitogenic pathways, including YAP, STAT3, IGFR1, and phospholipase C (PLC)/protein kinase C (PKC), were activated in both cancer types.
  • Identified numerous compensatory pathways contributing to drug tolerance.

Conclusions:

  • Effective strategies to prevent drug tolerance must address multiple alternative mitogenic pathways.
  • A single-pathway focus is insufficient for overcoming drug tolerance in cancer treatment.
Keywords:
acquired resistancedrug-tolerant cellspersisterstargeted therapies

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