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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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Toward a Better Understanding of the Complexity of Cancer Drug Resistance

Michael M Gottesman1, Orit Lavi1, Matthew D Hall1

  • 1Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; email: mgottesman@nih.gov , lavio@mail.nih.gov , hallma@mail.nih.gov.

Annual Review of Pharmacology and Toxicology
|October 31, 2015
PubMed

Insights

Anticancer drug resistance stems from complex genetic and cellular changes, alongside tumor microenvironment factors. Improving cancer treatment requires understanding these resistance mechanisms and developing better models.

Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Anticancer drug resistance is a significant challenge in cancer therapy.
  • It arises from multifaceted biological and physiological alterations within cancer cells and their environment.
  • Hallmarks of cancer, such as tumor heterogeneity and adaptability, contribute to resistance development.

Purpose of the Study:

  • To elucidate the complex mechanisms underlying anticancer drug resistance.
  • To highlight the role of cancer hallmarks in facilitating resistance.
  • To discuss strategies for overcoming drug resistance in cancer treatment.

Main Methods:

  • Review and synthesis of existing knowledge on cancer drug resistance mechanisms.
  • Analysis of how cancer hallmarks contribute to resistance.
  • Identification of limitations in current in vitro models for studying resistance.
  • Proposal of strategies to improve cancer treatment based on resistance mechanisms.

Main Results:

  • Drug resistance involves alterations in drug targets, alternative growth pathways, drug efflux, regulatory changes, and tumor microenvironment factors.
  • Cancer hallmarks like heterogeneity, pathway redundancy, and dynamic behavior facilitate these resistance mechanisms.
  • Current in vitro models inadequately mimic clinical cancer complexity, hindering resistance research.

Conclusions:

  • Understanding the intricate mechanisms of drug resistance is crucial for effective cancer therapy.
  • Addressing tumor heterogeneity and the dynamic nature of cancer is key to overcoming resistance.
  • Development of improved in vitro models is needed to better predict and combat clinical drug resistance.
Keywords:
ABCB1P-glycoproteinchemotherapymultidrug resistanceplatinum compounds

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