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Untangling the unfolded protein response

Emma L Davenport1, Gareth J Morgan, Faith E Davies

  • 1Section of Haemato-Oncology, The Institute of Cancer Research, Sutton, Surrey, UK.

Cell Cycle (Georgetown, Tex.)
|April 17, 2008
PubMed

Insights

Targeting heat shock proteins (HSP) and the unfolded protein response (UPR) simultaneously offers a novel cancer therapy strategy. This dual approach effectively kills cancer cells by disrupting essential survival pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Cancer cells rely on protein families like heat shock proteins (HSP) and the unfolded protein response (UPR) for survival under stress.
  • HSP90 stabilizes critical cancer survival factors such as AKT, ERB2, and HIF1alpha.
  • The UPR is crucial for protein folding and cellular adaptation to the hypoxic tumor microenvironment.

Purpose of the Study:

  • To investigate the potential of targeting HSP90 and UPR pathways simultaneously as a cancer treatment strategy.
  • To highlight the importance of targeting multiple signaling pathways for effective cancer cell killing, using multiple myeloma as a model.

Main Methods:

  • The study focuses on the roles of HSP90 and UPR in cancer cell survival.
  • It explores the implications of inhibiting HSP90 and UPR pathways.
  • The research is based on experimental work in multiple myeloma.

Main Results:

  • Inhibiting HSP90 destabilizes key cancer survival factors and can induce cell death by disrupting the UPR.
  • Targeting HSP90 presents a promising therapeutic strategy due to its role in stabilizing multiple cancer cell survival proteins.
  • Simultaneous targeting of HSP90 and UPR pathways demonstrates potential for effective cancer cell elimination.

Conclusions:

  • Targeting HSP90 inhibitors is a promising therapeutic avenue for a wide range of tumors.
  • Developing specific UPR inhibitors could also be of significant therapeutic interest.
  • Simultaneous targeting of multiple signaling pathways, exemplified by HSP and UPR, is crucial for effectively killing cancer cells.

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