Stromal barriers within the tumor microenvironment and obstacles to nanomedicine

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Nanomedicine has been heralded as the elusive “magic bullet” of cancer chemotherapeutics ever since the description of the Enhanced Permeability and Retention (EPR) effect in 1986. However, decades of research have often shown a great discrepancy between the salient effects seen in preclinical models and the suboptimal effects seen in clinical trials. This indicates that various obstacles exist within human tumors that impede the delivery and penetration of nanomedicine and that the EPR effect itself may be necessary but not sufficient for an efficacious nanomedicine formulation. Furthermore, these obstacles may be absent or much weaker in often used preclinical models, pointing at the importance of developing novel, clinically relevant preclinical models for testing the efficacy of nanomedicine. It is becoming increasingly clear that the various cellular and extracellular matrix components of the tumor stroma that together consist the tumor microenvironment (TME) play an important role in determining the efficiency of nanomedicine penetration into the tumor. We refer to the impediments that these stromal components of the TME pose to nanomedicine as “stromal barriers”. In this chapter, we review the factors affecting nanomedicine delivery with a particular emphasis on the stromal barriers within the TME. We also review the preclinical models available for testing the efficacy of nanomedicine, and how novel models might be developed to further our understanding of the principles governing nanomedicine delivery and penetration into tumors.

Original languageEnglish
Title of host publicationCancer Drug Delivery Systems Based on the Tumor Microenvironment
PublisherSpringer Japan
Pages57-89
Number of pages33
ISBN (Electronic)9784431568803
ISBN (Print)9784431568780
DOIs
Publication statusPublished - Jan 1 2020

Keywords

  • Enhanced permeability and retention (EPR) effect
  • Nanomedicine delivery
  • Stromal barriers
  • Tumor microenvironment

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Engineering(all)

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  • Cite this

    Tanaka, H. Y., & Kano, M. R. (2020). Stromal barriers within the tumor microenvironment and obstacles to nanomedicine. In Cancer Drug Delivery Systems Based on the Tumor Microenvironment (pp. 57-89). Springer Japan. https://doi.org/10.1007/978-4-431-56880-3_4