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Updated: Mar 5, 2026

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

Published on: December 9, 2015

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Molecular and Pharmacological Mechanisms of Drug Resistance:An Evolving Paradigm

Benedetta Colmegna1, Lavinia Morosi1, Maurizio D'Incalci2

  • 1Department of Oncology, IRCCS 'Mario Negri', Institute for Pharmacological Research, 20145, Milan, Italy.

Handbook of Experimental Pharmacology
|March 24, 2017
PubMed

Insights

Tumor cells develop resistance to anticancer drugs through various mechanisms, including altered drug metabolism, transport, and target modification. Poor drug distribution, due to tumor vascularization issues, also contributes significantly to treatment failure.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Biology

Background:

  • Malignant tumors exhibit high heterogeneity and genomic instability.
  • This complexity leads to intrinsic or acquired resistance to anticancer therapies.
  • Understanding resistance mechanisms is crucial for improving cancer treatment efficacy.

Purpose of the Study:

  • To elucidate the multifaceted mechanisms underlying cancer cell resistance to anticancer drugs.
  • To highlight the role of tumor microenvironment and pharmacokinetics in treatment failure.

Main Methods:

  • Review of existing literature on cancer drug resistance.
  • Analysis of molecular and cellular mechanisms of resistance.
  • Examination of pharmacokinetic and pharmacodynamic factors influencing drug efficacy.

Main Results:

  • Resistance arises from intracellular drug inactivation, altered drug transport (uptake/efflux), and target modifications.
  • Inefficient drug distribution, caused by poor tumor vascularization and high interstitial pressure, is a key factor.
  • Activation of anti-apoptotic and cell survival pathways, often supported by the tumor microenvironment, promotes resistance.

Conclusions:

  • Cancer drug resistance is a complex interplay of tumor cell-intrinsic factors and extrinsic influences.
  • Addressing pharmacokinetic challenges and the tumor microenvironment is essential for overcoming resistance.
  • Further research into combination therapies targeting multiple resistance pathways is warranted.
Keywords:
ApoptosisDrug distributionMass spectrometry imagingMultidrug resistancePharmacokinetics

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