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Updated: Jun 21, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Drug resistance and the solid tumor microenvironment

Olivier Trédan1, Carlos M Galmarini, Krupa Patel

  • 1Division of Applied Molecular Oncology and Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Ave, Toronto, ON M5G 2M9, Canada.

Journal of the National Cancer Institute
|September 27, 2007
PubMed

Insights

Solid tumors often resist chemotherapy due to poor drug penetration and the tumor microenvironment. Strategies targeting the tumor microenvironment can improve anticancer drug effectiveness.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Anticancer drug resistance in human tumors is commonly attributed to cellular mechanisms like gene mutations.
  • However, limited drug penetration into tumor tissue is a significant, often overlooked, cause of treatment failure.
  • The tumor microenvironment, characterized by gradients in proliferation, hypoxia, and acidity, further complicates drug delivery and efficacy.

Purpose of the Study:

  • To review the role of the tumor microenvironment in solid tumor resistance to chemotherapy.
  • To discuss strategies for overcoming drug resistance by targeting the tumor microenvironment.

Main Methods:

  • Literature review of studies investigating drug penetration and tumor microenvironment factors in cancer therapy.
  • Analysis of mechanisms by which tumor microenvironment characteristics influence drug sensitivity and resistance.

Main Results:

  • Inefficient drug delivery through tumor vasculature and tissue penetration limits drug concentration at the target site.
  • Tumor microenvironment heterogeneity, including hypoxia and acidity, creates localized regions of reduced drug sensitivity.
  • These factors contribute significantly to overall treatment failure in solid tumors.

Conclusions:

  • The tumor microenvironment plays a critical role in anticancer drug resistance beyond cellular mechanisms.
  • Modifying the tumor microenvironment presents a promising therapeutic strategy to enhance chemotherapy effectiveness.
  • Targeting drug delivery and microenvironment factors could improve outcomes for patients with solid tumors.

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