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PI3K Targeting in Non-solid Cancer

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PI3K and AKT Isoforms in Immunity

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 436))

Abstract

Despite the therapeutic progress, relapse remains a major problem in the treatment of acute lymphoblastic leukemia (ALL). Most leukemia cells that survive chemotherapy are found in the bone marrow (BM), thus resistance to chemotherapy and other treatments may be partially attributed to pro-survival signaling to leukemic cells mediated by leukemia cell-microenvironment interactions. Adhesion of leukemia cells to BM stromal cells may lead to cell adhesion-mediated drug resistance (CAM-DR) mediating intracellular signaling changes that support survival of leukemia cells. In ALL and chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the PI3K/AKT signaling pathway has been shown to be critical in CAM-DR. PI3K targeting inhibitors have been approved for CLL and have been evaluated preclinically in ALL. However, PI3K inhibition has yet to be approved for clinical use in ALL. Here, we review the role of PI3K signaling for normal hematopoietic and leukemia cells and summarize preclinical inhibitors of PI3K in ALL.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

BM:

Bone marrow

CAM-DR:

Cell adhesion mediated drug resistance

CLL:

Chronic lymphocytic leukemia

PI3K:

Phosphoinotiside-3 kinase

RTK:

Receptor tyrosine kinases

GPCRS:

G-protein coupled receptors

PIP2:

Phosphatidylinositol-diphosphate

PIP3:

Phosphatidylinositol-triphosphate

PTEN:

Phosphatase and tensin homolog deleted from chromosome 10

PDK1:

Phosphoinositide-dependent kinase 1

MSC:

Mesenchymal stem cells

T-ALL:

T cell acute lymphoblastic leukemia

CNS:

Central nervous system

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Acknowledgements

NIH RO1 CA172896 and Curing Kids’ Cancer Award to Y.K.

Author Contributions

Writing—Original Draft Preparation, HNK, and YMK.; Writing—Review and Editing: HNK, HAO, VS, CN, and YMK.

Conflicts of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

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

    Hye Na Kim, Heather Ogana, Vanessa Sanchez, Cydney Nichols & Yong-Mi Kim

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  1. Hye Na Kim
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  2. Heather Ogana
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  3. Vanessa Sanchez
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  4. Cydney Nichols
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Correspondence to Yong-Mi Kim .

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  1. Faculty of Medicine, Imperial College London, London, UK

    Margarita Dominguez-Villar

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Kim, H.N., Ogana, H., Sanchez, V., Nichols, C., Kim, YM. (2022). PI3K Targeting in Non-solid Cancer. In: Dominguez-Villar, M. (eds) PI3K and AKT Isoforms in Immunity . Current Topics in Microbiology and Immunology, vol 436. Springer, Cham. https://doi.org/10.1007/978-3-031-06566-8_17

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