Combination regimens with single specificity inhibitors
| Target . | Compound . | Combination regimens . | Effects . | Clinical trials (phase) . | Leukemia . | Reference(s) . | |
|---|---|---|---|---|---|---|---|
| In vitro . | In vivo . | ||||||
| PI3K | Wortmannin | ATRA (DA) | + | − | 159 | ||
| STI-571 (Bcr-Abl TKI) | + | − | 141 | ||||
| LY294002 | Apigenin (CK2 I) | + | − | 160 | |||
| ATRA (DA) | + | − | 159 | ||||
| STI-571 (Bcr-Abl TKI) | + | − | 141 | ||||
| Arsenic trioxide | + | − | 161 | ||||
| p110δ | IC87114 | VP16 (CT) | + | − | 145 | ||
| CAL-101 | Lenalidomide | + | − | 98 | |||
| CT and mAb CD20 | − | − | NCT01088048 (1) | CLL | |||
| Rituximab (mAb CD20) | − | − | NCT01203930 (2) | CLL | |||
| PDK1 | UCN-01 | Ara-C (CT) | + | − | (2) | AML | 146 |
| Cytarabine (CT) | − | − | NCT00004263 (1) | AML and MDS | |||
| Fludarabine (CT) | − | − | NCT00019838 (1) | RRL | |||
| OSU-03012 | STI-571 (Bcr-Abl TKI) | + | − | 140 | |||
| PP2A | Forskolin | Idarubicin/Ara-C | + | − | 162 | ||
| PKB | Perifosine | UCN-01 | − | − | NCT00301938 (1) | RRL | |
| HDAC I | + | − | 130 | ||||
| TRAIL (AI) | + | − | 163 | ||||
| Etoposide (CT | + | − | 103 | ||||
| PIA | CT | + | − | 104 | |||
| Triciribine | Cytarabine (CT) | + | − | 106 | |||
| MK2206 | Rituximab (mAb CD20) | − | − | NCT01369849 (1/2) | CLL | ||
| Arsenic trioxide | + | − | 161 | ||||
| mTOR | Rapamycin | UCN-01 | + | − | 122 | ||
| 3-BrOP (glycolysis I) | + | − | 164 | ||||
| STI-571 (Bcr-Abl TKI) | + | − | 139 | ||||
| Notch I | + | − | 165 | ||||
| Erlotinib (EGFR-TKI) | + | − | 166 | ||||
| Curcumin | + | − | 167 | ||||
| Dexamethasone | + | − | 168,169 | ||||
| Etoposide (CT) | + | + | 144 | ||||
| Decatibine (CT) | − | − | NCT00861874 (1) | AML | |||
| Aracytin (CT) | − | − | NCT00235560 (2) | AML | |||
| Methotrexate (CT) | + | + | NCT01162551 (2) | ALL and CLL | 111 | ||
| Anthracyclin (CT) | + | − | 170 | ||||
| Daunorubicin (CT) | + | − | 171 | ||||
| CT | + | − | NCT00776373 (1/2) | ALL and CML | 152 | ||
| + | − | NCT01184898 (1/2) | AML | 152 | |||
| + | − | NCT00780104 (1/2) | AML and CML | 152 | |||
| RAD001 | IC87114 | + | − | 114 | |||
| BAG956 | + | + | 121 | ||||
| Bortezomib (PI) | + | − | 132 | ||||
| MS-275 (HDAC I) | + | + | 129 | ||||
| PKC412 (Flt3 TKI) | − | − | NCT00819546 (1) | AML and MDS | |||
| Imatinib (Bcr-Abl TKI) | + | − | NCT00093639 (1/2) | CML | 138 | ||
| + | − | NCT01188889 (1/2) | CML | 138 | |||
| Nilotinib (c-Kit-TKI) | − | − | NCT00762632 (1/2) | AML | |||
| Alemtuzumab (mAb CD52) | − | − | NCT00935792 (1/2) | CLL | |||
| ATRA (DA) | + | + | 172 | ||||
| Ara-C (CT) | + | − | 132,149 | ||||
| Vincristine (CT) | + | + | 173 | ||||
| CT | − | − | NCT00544999 (1) | AML | |||
| − | − | NCT01154439 (1) | AML | ||||
| CCI-779 | Methotrexate (CT) | + | + | 111 | |||
| Clofarabine (CT) | − | − | NCT00775593 (2) | AML | |||
| STI-571 (Bcr-Abl TKI) | − | − | NCT00101088 (1) | CML | |||
| PP242 | Vincristine (CT) | + | − | 118 | |||
| OSI-027 | STI-571 (Bcr-Abl TKI) | + | − | 119 | |||
| GILZ | STI-571 (Bcr-Abl TKI) | + | − | 137 | |||
| Target . | Compound . | Combination regimens . | Effects . | Clinical trials (phase) . | Leukemia . | Reference(s) . | |
|---|---|---|---|---|---|---|---|
| In vitro . | In vivo . | ||||||
| PI3K | Wortmannin | ATRA (DA) | + | − | 159 | ||
| STI-571 (Bcr-Abl TKI) | + | − | 141 | ||||
| LY294002 | Apigenin (CK2 I) | + | − | 160 | |||
| ATRA (DA) | + | − | 159 | ||||
| STI-571 (Bcr-Abl TKI) | + | − | 141 | ||||
| Arsenic trioxide | + | − | 161 | ||||
| p110δ | IC87114 | VP16 (CT) | + | − | 145 | ||
| CAL-101 | Lenalidomide | + | − | 98 | |||
| CT and mAb CD20 | − | − | NCT01088048 (1) | CLL | |||
| Rituximab (mAb CD20) | − | − | NCT01203930 (2) | CLL | |||
| PDK1 | UCN-01 | Ara-C (CT) | + | − | (2) | AML | 146 |
| Cytarabine (CT) | − | − | NCT00004263 (1) | AML and MDS | |||
| Fludarabine (CT) | − | − | NCT00019838 (1) | RRL | |||
| OSU-03012 | STI-571 (Bcr-Abl TKI) | + | − | 140 | |||
| PP2A | Forskolin | Idarubicin/Ara-C | + | − | 162 | ||
| PKB | Perifosine | UCN-01 | − | − | NCT00301938 (1) | RRL | |
| HDAC I | + | − | 130 | ||||
| TRAIL (AI) | + | − | 163 | ||||
| Etoposide (CT | + | − | 103 | ||||
| PIA | CT | + | − | 104 | |||
| Triciribine | Cytarabine (CT) | + | − | 106 | |||
| MK2206 | Rituximab (mAb CD20) | − | − | NCT01369849 (1/2) | CLL | ||
| Arsenic trioxide | + | − | 161 | ||||
| mTOR | Rapamycin | UCN-01 | + | − | 122 | ||
| 3-BrOP (glycolysis I) | + | − | 164 | ||||
| STI-571 (Bcr-Abl TKI) | + | − | 139 | ||||
| Notch I | + | − | 165 | ||||
| Erlotinib (EGFR-TKI) | + | − | 166 | ||||
| Curcumin | + | − | 167 | ||||
| Dexamethasone | + | − | 168,169 | ||||
| Etoposide (CT) | + | + | 144 | ||||
| Decatibine (CT) | − | − | NCT00861874 (1) | AML | |||
| Aracytin (CT) | − | − | NCT00235560 (2) | AML | |||
| Methotrexate (CT) | + | + | NCT01162551 (2) | ALL and CLL | 111 | ||
| Anthracyclin (CT) | + | − | 170 | ||||
| Daunorubicin (CT) | + | − | 171 | ||||
| CT | + | − | NCT00776373 (1/2) | ALL and CML | 152 | ||
| + | − | NCT01184898 (1/2) | AML | 152 | |||
| + | − | NCT00780104 (1/2) | AML and CML | 152 | |||
| RAD001 | IC87114 | + | − | 114 | |||
| BAG956 | + | + | 121 | ||||
| Bortezomib (PI) | + | − | 132 | ||||
| MS-275 (HDAC I) | + | + | 129 | ||||
| PKC412 (Flt3 TKI) | − | − | NCT00819546 (1) | AML and MDS | |||
| Imatinib (Bcr-Abl TKI) | + | − | NCT00093639 (1/2) | CML | 138 | ||
| + | − | NCT01188889 (1/2) | CML | 138 | |||
| Nilotinib (c-Kit-TKI) | − | − | NCT00762632 (1/2) | AML | |||
| Alemtuzumab (mAb CD52) | − | − | NCT00935792 (1/2) | CLL | |||
| ATRA (DA) | + | + | 172 | ||||
| Ara-C (CT) | + | − | 132,149 | ||||
| Vincristine (CT) | + | + | 173 | ||||
| CT | − | − | NCT00544999 (1) | AML | |||
| − | − | NCT01154439 (1) | AML | ||||
| CCI-779 | Methotrexate (CT) | + | + | 111 | |||
| Clofarabine (CT) | − | − | NCT00775593 (2) | AML | |||
| STI-571 (Bcr-Abl TKI) | − | − | NCT00101088 (1) | CML | |||
| PP242 | Vincristine (CT) | + | − | 118 | |||
| OSI-027 | STI-571 (Bcr-Abl TKI) | + | − | 119 | |||
| GILZ | STI-571 (Bcr-Abl TKI) | + | − | 137 | |||
DA indicates differentiating agents; TKI, tyrosine kinase inhibitor; I, inhibitor; CT, chemotherapy; AI, apoptosis inducer; RRL, relapsed and refractory leukemia; and PI, proteasome inhibitor.