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PI3K Targeting in Non-solid Cancer.

Hye Na Kim1, Heather Ogana1, Vanessa Sanchez1

  • 1Department of Pediatrics, Division of Hematology and Oncology, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA.

Current Topics in Microbiology and Immunology
|October 15, 2022
PubMed
Summary

Relapse in acute lymphoblastic leukemia (ALL) is linked to leukemia cells resisting chemotherapy in the bone marrow. Targeting the PI3K/AKT pathway shows promise for overcoming this drug resistance in ALL treatment.

Keywords:
Acute lymphoblastic leukemia (ALL)Cell adhesion mediated drug resistance (CAM-DR)PI3K/AKTPI3KγPI3Kδ

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Relapse remains a significant challenge in acute lymphoblastic leukemia (ALL) treatment, with surviving leukemia cells often residing in the bone marrow.
  • Leukemia cell-microenvironment interactions, particularly adhesion to bone marrow stromal cells, contribute to chemotherapy resistance via cell adhesion-mediated drug resistance (CAM-DR).
  • The PI3K/AKT signaling pathway is critically involved in CAM-DR in both ALL and chronic lymphocytic leukemia (CLL).

Purpose of the Study:

  • To review the role of PI3K signaling in normal hematopoietic cells and leukemia cells.
  • To summarize preclinical PI3K inhibitors evaluated for ALL treatment.
  • To highlight the potential of PI3K inhibition in overcoming drug resistance in ALL.

Main Methods:

  • Literature review of studies investigating PI3K signaling in hematopoiesis and leukemia.
  • Summary of preclinical research on PI3K inhibitors in ALL models.
  • Analysis of the role of cell adhesion-mediated drug resistance (CAM-DR) in ALL.

Main Results:

  • PI3K/AKT pathway activation is crucial for CAM-DR, promoting leukemia cell survival.
  • PI3K inhibitors have shown efficacy in preclinical ALL studies.
  • While approved for CLL, PI3K inhibitors are not yet clinically approved for ALL.

Conclusions:

  • Targeting the PI3K/AKT pathway represents a promising therapeutic strategy to overcome chemotherapy resistance in ALL.
  • Further clinical evaluation of PI3K inhibitors is warranted for ALL treatment.
  • Understanding leukemia cell-microenvironment interactions is key to developing effective ALL therapies.