TY - JOUR

T1 - Targeting of PI3K/AKT signaling and DNA damage response in acute myeloid leukemia

T2 - a novel therapeutic strategy to boost chemotherapy response and overcome resistance

AU - Estruch, Montserrat

AU - Vittori, Camilla

AU - Montesinos, Teresa Muñoz

AU - Reckzeh, Kristian

AU - Theilgaard-Mönch, Kim

PY - 2021

Y1 - 2021

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.

U2 - 10.20517/cdr.2021.76

DO - 10.20517/cdr.2021.76

M3 - Journal article

C2 - 35582388

VL - 4

SP - 984

EP - 995

JO - Cancer Drug Resistance

JF - Cancer Drug Resistance

SN - 2578-532X

ER -