Table 3

Investigational approaches (selection)

Mode of actionAgent(s)PhaseTarget(s)
Third-generation TKI Ponatinib53  II Pan-BCR-ABL including T315I 
 DCC-203672  Abl-switch pocket 
PP2A activation Fingolimod (FTY720)75  Preclinical PP2A 
 SET antagonist OP44976  Preclinical SET 
 CIP2A inhibitor74  Preclinical CIP2A 
Survival of LSCs BCL6 + TK inhibitors78  Preclinical BCL6 + BCR-ABL 
 HIF1α inhibitor80  Preclinical HIF1α 
 IL1 RAP antibodies86  Preclinical IL1 RAP 
 Smoothened inhibitors in combination with TKI83  (dasatinib, nilotinib) Preclinical Smoothened (hedgehog pathway) + BCR-ABL 
 Jak2 inhibitor + dasatinib85  Preclinical Jak2 + BCR-ABL, LSC 
Activation of apoptosis BCL2-inhibitor ABT-73788  Preclinical Antiapoptotic proteins 
 Triptolide87,88  Preclinical Antiapoptotic proteins 
 Dual-kinase inhibitor ON04458091  Preclinical BC, T315I 
 MEK inhibitor PD184352 + farnesyltransferase inhibitor BMS-21466289  Preclinical MEK1, MEK2, RAS 
Others Omacetaxine92  II / III BCR-ABL, T315I, BC 
Mode of actionAgent(s)PhaseTarget(s)
Third-generation TKI Ponatinib53  II Pan-BCR-ABL including T315I 
 DCC-203672  Abl-switch pocket 
PP2A activation Fingolimod (FTY720)75  Preclinical PP2A 
 SET antagonist OP44976  Preclinical SET 
 CIP2A inhibitor74  Preclinical CIP2A 
Survival of LSCs BCL6 + TK inhibitors78  Preclinical BCL6 + BCR-ABL 
 HIF1α inhibitor80  Preclinical HIF1α 
 IL1 RAP antibodies86  Preclinical IL1 RAP 
 Smoothened inhibitors in combination with TKI83  (dasatinib, nilotinib) Preclinical Smoothened (hedgehog pathway) + BCR-ABL 
 Jak2 inhibitor + dasatinib85  Preclinical Jak2 + BCR-ABL, LSC 
Activation of apoptosis BCL2-inhibitor ABT-73788  Preclinical Antiapoptotic proteins 
 Triptolide87,88  Preclinical Antiapoptotic proteins 
 Dual-kinase inhibitor ON04458091  Preclinical BC, T315I 
 MEK inhibitor PD184352 + farnesyltransferase inhibitor BMS-21466289  Preclinical MEK1, MEK2, RAS 
Others Omacetaxine92  II / III BCR-ABL, T315I, BC 

LSC indicates leukemia stem cell; and MEK, mitogen-activated protein kinase kinase.

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