PMID- 36243854
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20230411
IS  - 0070-217X (Print)
IS  - 2196-9965 (Electronic)
IS  - 0070-217X (Linking)
VI  - 436
DP  - 2022
TI  - PI3K Targeting in Non-solid Cancer.
PG  - 393-407
LID - 10.1007/978-3-031-06566-8_17 [doi]
AB  - 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.
CI  - (c) 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.
FAU - Kim, Hye Na
AU  - Kim HN
AD  - Department of Pediatrics, Division of Hematology and Oncology, Children's 
      Hospital Los Angeles, University of Southern California, Los Angeles, California, 
      USA.
FAU - Ogana, Heather
AU  - Ogana H
AD  - Department of Pediatrics, Division of Hematology and Oncology, Children's 
      Hospital Los Angeles, University of Southern California, Los Angeles, California, 
      USA.
FAU - Sanchez, Vanessa
AU  - Sanchez V
AD  - Department of Pediatrics, Division of Hematology and Oncology, Children's 
      Hospital Los Angeles, University of Southern California, Los Angeles, California, 
      USA.
FAU - Nichols, Cydney
AU  - Nichols C
AD  - Department of Pediatrics, Division of Hematology and Oncology, Children's 
      Hospital Los Angeles, University of Southern California, Los Angeles, California, 
      USA.
FAU - Kim, Yong-Mi
AU  - Kim YM
AD  - Department of Pediatrics, Division of Hematology and Oncology, Children's 
      Hospital Los Angeles, University of Southern California, Los Angeles, California, 
      USA. ymkim@chla.usc.edu.
LA  - eng
GR  - R01 CA172896/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Curr Top Microbiol Immunol
JT  - Current topics in microbiology and immunology
JID - 0110513
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Humans
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - Tumor Microenvironment
PMC - PMC10075235
MID - NIHMS1856139
OTO - NOTNLM
OT  - Acute lymphoblastic leukemia (ALL)
OT  - Cell adhesion mediated drug resistance (CAM-DR)
OT  - PI3K/AKT
OT  - PI3Kgamma
OT  - PI3Kdelta
COIS- Conflicts of Interest The authors declare no conflict of interest.
EDAT- 2022/10/16 06:00
MHDA- 2022/10/19 06:00
PMCR- 2023/04/05
CRDT- 2022/10/15 23:30
PHST- 2022/10/15 23:30 [entrez]
PHST- 2022/10/16 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2023/04/05 00:00 [pmc-release]
AID - 10.1007/978-3-031-06566-8_17 [doi]
PST - ppublish
SO  - Curr Top Microbiol Immunol. 2022;436:393-407. doi: 10.1007/978-3-031-06566-8_17.