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Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma
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The great escape: How metastases of melanoma, and other carcinomas, avoid elimination

Alan Wells1,2,3,4,5, Amanda Clark1, Andrew Bradshaw1,3

  • 11 Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Experimental Biology and Medicine (Maywood, N.J.)
|February 16, 2019
PubMed
Abstract

Insights

Metastatic cancers resist therapies due to intrinsic and extrinsic changes promoting survival. This study proposes a framework for understanding microenvironmental factors driving this generalized therapeutic resistance in disseminated tumor cells.

Area of Science:

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment

Background:

  • Metastatic cancer poses a significant challenge due to resistance to systemic therapies.
  • Targeted and immunomodulatory treatments have shown limited success in overcoming this resistance.
  • Both cancer-intrinsic and cancer-extrinsic alterations contribute to the survival of disseminated tumor cells.

Purpose of the Study:

  • To present a novel conceptual framework for understanding the microenvironmental contributions to generalized therapeutic resistance in metastatic cancer.
  • To highlight the role of microenvironmental inputs and changes in promoting survival of disseminated tumor cells.
  • To discuss experimental systems for studying therapeutic resistance, including their advantages and limitations.

Main Methods:

  • Conceptual framework development.
  • Literature review and synthesis of existing findings.
  • Analysis of cancer-intrinsic and -extrinsic factors.

Main Results:

  • A conceptual framework is proposed detailing microenvironmental influences on therapeutic resistance.
  • Identified cancer-intrinsic and -extrinsic changes confer survival advantages to disseminated tumor cells.
  • Critically evaluated experimental systems for studying generalized therapeutic resistance.

Conclusions:

  • Generalized therapeutic resistance in metastatic cancer is driven by complex microenvironmental interactions.
  • Understanding these microenvironmental factors is crucial for developing effective cancer therapies.
  • Further research into the tumor microenvironment is essential to combat cancer mortality.
Keywords:
Liver metastasishepatic nichemetastatic modelsmicrophysiologicaltumor microenvironment

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