TY - JOUR
T1 - Targeting of PI3K/AKT signaling and DNA damage response in acute myeloid leukemia: a novel therapeutic strategy to boost chemotherapy response and overcome resistance
AU - Alrich, Montserrat Estruch
AU - Vittori, Camilla
AU - Muños-Montesinos, Teresa
AU - Reckzeh, Kristian
AU - Theilgaard-Mönch, Kim
PY - 2021/11/10
Y1 - 2021/11/10
N2 - Resistance of cancer patients to DNA damaging radiation therapy and chemotherapy remains a major problem in the clinic. The current review discusses the molecular mechanisms of therapy resistance in acute myeloid leukemia (AML) conferred by cooperative chemotherapy-induced DNA damage response (DDR) and mutational activation of PI3K/AKT signaling. In addition, strategies to overcome resistance are discussed, with particular focus on studies underpinning the vast potential of therapies combining standard chemotherapy AML regimens with small molecule inhibitors targeting key regulatory hubs at the interface of DDR and oncogenic signaling pathways.
AB - Resistance of cancer patients to DNA damaging radiation therapy and chemotherapy remains a major problem in the clinic. The current review discusses the molecular mechanisms of therapy resistance in acute myeloid leukemia (AML) conferred by cooperative chemotherapy-induced DNA damage response (DDR) and mutational activation of PI3K/AKT signaling. In addition, strategies to overcome resistance are discussed, with particular focus on studies underpinning the vast potential of therapies combining standard chemotherapy AML regimens with small molecule inhibitors targeting key regulatory hubs at the interface of DDR and oncogenic signaling pathways.
KW - AML
KW - Chemotherapy
KW - DNA damage response
KW - PI3K/AKT
KW - Resistance
UR - http://www.scopus.com/inward/record.url?scp=85123370145&partnerID=8YFLogxK
U2 - 10.20517/cdr.2021.76
DO - 10.20517/cdr.2021.76
M3 - Review
C2 - 35582388
SN - 2578-532X
VL - 4
SP - 984
EP - 995
JO - Cancer Drug Resistance
JF - Cancer Drug Resistance
IS - 4
ER -