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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
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A new strategy to ERADicate HER2-positive breast tumors?

Sanjeevani Arora1, Erica A Golemis2

  • 1Program in Molecular Therapeutics, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Science Signaling
|May 28, 2015
PubMed

Insights

HER2-positive breast cancers resistant to HER2-targeting agents show increased endoplasmic reticulum-associated degradation (ERAD). Targeting ERAD with HER2-dependent signaling may offer new treatment options for this challenging breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • HER2-positive breast cancers often develop resistance to HER2-targeting therapies like trastuzumab.
  • Limited treatment options exist for patients with HER2-positive breast cancer resistant to standard therapies.

Purpose of the Study:

  • To investigate the mechanisms underlying resistance to HER2-targeting agents in breast cancer.
  • To identify novel therapeutic strategies for HER2-positive breast tumors that have become resistant to treatment.

Main Methods:

  • Analysis of HER2-positive tumors for alterations in cellular stress response pathways.
  • Investigation of the role of the endoplasmic reticulum-associated degradation (ERAD) system in treatment resistance.

Main Results:

  • HER2-positive tumors exhibit a characteristic increase in the endoplasmic reticulum-associated degradation (ERAD) system.
  • This ERAD system activation serves as a mechanism to relieve proteotoxic stress within the cancer cells.

Conclusions:

  • Targeted disruption of ERAD signaling, in combination with HER2-dependent signaling pathways, presents a potential synthetic lethality approach.
  • This strategy may significantly improve the therapeutic management of HER2-positive breast cancers resistant to current treatments.

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