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Microenvironment-mediated resistance to anticancer therapies

Oakley C Olson1, Johanna A Joyce

  • 1Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

Cell Research
|September 5, 2012
PubMed

Insights

Tumor cells can develop resistance to targeted therapies through genomic changes. However, external factors like HGF from the tumor microenvironment can also drive resistance to BRAF and HER2 inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Resistance to molecularly targeted therapies is a significant clinical challenge.
  • Genomic alterations within tumor cells are known to cause resistance by reactivating oncogenic signaling pathways.
  • Tumor cell-extrinsic mechanisms of resistance are less understood.

Purpose of the Study:

  • To investigate the role of tumor microenvironment in mediating resistance to targeted therapies.
  • To identify soluble factors involved in paracrine resistance mechanisms.

Main Methods:

  • Review of recent studies identifying HGF as a resistance mediator.
  • Analysis of paracrine signaling pathways involved in targeted therapy resistance.

Main Results:

  • HGF (hepatocyte growth factor) has been identified as a key soluble factor.
  • HGF mediates resistance to BRAF and HER2 inhibitors.
  • Resistance is mediated in a paracrine manner, involving cell-to-cell communication.

Conclusions:

  • The tumor microenvironment plays a crucial role in acquired resistance to targeted therapies.
  • HGF signaling represents a potential therapeutic target to overcome resistance.
  • Understanding extrinsic resistance mechanisms is vital for improving cancer treatment strategies.

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