Ex vivo treatment response of primary tumors and/or associated metastases for preclinical and clinical development of therapeutics

J Vis Exp. 2014 Oct 2:(92):e52157. doi: 10.3791/52157.

Abstract

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Drug Screening Assays, Antitumor / methods*
  • Humans
  • Microtomy / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / pathology*
  • Tissue Culture Techniques / methods*
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents