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Targeting the integrated stress response in hematologic malignancies

Gus O Nwosu1, Jason A Powell2,3, Stuart M Pitson4,5,6

  • 1Centre for Cancer Biology, University of South Australia and SA Pathology, UniSA Bradley Building, North Tce, Adelaide, SA, 5001, Australia.

Experimental Hematology & Oncology
|November 9, 2022
PubMed

Insights

Targeted therapies for blood cancers face resistance. The integrated stress response (ISR) pathway is a promising new target for overcoming this resistance and improving cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Targeted therapies are vital for hematologic malignancies but face significant resistance.
  • Acquired or intrinsic resistance limits the effectiveness of current treatments.
  • Novel therapeutic targets are needed to improve patient outcomes.

Purpose of the Study:

  • To review the role of the integrated stress response (ISR) in hematologic malignancies.
  • To explore the ISR's involvement in targeted therapy mechanisms.
  • To highlight the ISR as a target for novel therapeutic strategies.

Main Methods:

  • Literature review of the integrated stress response in hematologic cancers.
  • Analysis of ISR's role in targeted therapy resistance.
  • Discussion of pharmacologic modulation of the ISR.

Main Results:

  • The ISR is activated in cancer cells due to dysregulated growth, metabolism, and therapy exposure.
  • The ISR plays a critical role in the efficacy and resistance of targeted therapies.
  • Pharmacologic targeting of the ISR presents a novel strategy.

Conclusions:

  • The integrated stress response is a key pathway in hematologic malignancies.
  • Modulating the ISR can overcome resistance to targeted therapies.
  • Targeting the ISR offers a promising avenue for improved hematologic cancer treatment.
Keywords:
ATF4GCN2HRIHematological malignancyIntegrated stress responsePERKPKRTargeted therapy

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