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Updated: Sep 4, 2025

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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Establishment of In Vivo Acquired Resistance to Chemotherapy Via Individual Dose Escalation Treatment Regime

Karen T Barker1, Orli Yogev2

  • 1Division of Clinical Studies, The Institute of Cancer Research, London, UK.

Methods in Molecular Biology (Clifton, N.J.)
|July 22, 2022
PubMed

Insights

Developing new cancer drugs is challenging due to drug resistance. This study presents a novel in vivo model that accurately mimics relapsed cancer, aiding the creation of more effective treatments.

Area of Science:

  • Oncology
  • Preclinical Cancer Models
  • Drug Resistance Research

Background:

  • Drug resistance is a major cause of cancer mortality.
  • Current preclinical models inadequately represent relapsed disease and the tumor microenvironment.
  • There is a critical need for advanced models to develop novel cancer therapeutics.

Purpose of the Study:

  • To develop an in vivo assay that models the acquisition of drug resistance.
  • To create a preclinical model that incorporates the tumor microenvironment and structure.
  • To establish a reliable tool for developing new therapies for relapsed cancers.

Main Methods:

  • An in vivo dose-escalation protocol was developed to model acquired resistance.
  • A chemo-resistant neuroblastoma model was generated.
  • The model's characteristics, including metastases and genetic signature, were analyzed.

Main Results:

  • The developed in vivo protocol successfully modeled the acquisition of drug resistance.
  • The chemo-resistant neuroblastoma model exhibited metastases and a genetic profile similar to clinical relapsed tumors.
  • The model demonstrated the importance of the tumor microenvironment in resistance.

Conclusions:

  • The novel in vivo dose-escalation protocol provides a faithful model for studying acquired drug resistance.
  • This model can be adapted for various relapsed diseases, improving preclinical research.
  • The developed assay serves as a valuable tool for advancing novel cancer therapy development.
Keywords:
Acquired resistanceCyclophosphamideDose escalationDrug resistanceNeuroblastoma

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