|
Inhibitor of oncogenic driver
(target; drug) | Induction of mitochondrial addiction | Mechanism(s) of mitochondrial activation | Combination (target; drug) | Cancer type; cell type; experimental models | Anticancer effects on cells resistant to targeted therapy | Reference |
|
PI3K inhibitor;
PX-866 | + | Paradoxical activation of mitochondrial Akt2 and thereby of cyclophilin D phosphorylation | Cyclophilin D inhibitor;
Gamitrinib | Glioblastoma, breast and lung adenocarcinoma;
cell lines and patient organotypic culture;
in vitro and in vivo (xenograft models) | nd | [34] |
|
| MEK inhibitor; Selumetinib | +/− | MITF-PGC-1α axis regulated by mTORC1/2 | mTORC1/2 inhibitor;
AZD 8055 | Subpopulation of melanoma with high levels of OXPHOS;
cell lines and tumor biopsies;
in vitro and in vivo (xenograft models) | + | [35] |
|
| TKI such as BCRABL inhibitor (imatinib) or FLT3 inhibitor (quirzatinib) | + | Pyruvate entry in the TCA cycle | Oligomycin A
(at low nmol/L concentrations) | BCRABL+ CM leukemia
FLT3 ITD AML;
cell lines;
in vitro and in vivo (mouse leukemia models) | nd | [36] |
|
| MEK inhibitor (AZD8330) and dual PI3K/mTOR inhibitor (BEZ235) | + | Mitochondrial biogenesis and activity | Oligomycin A | Pancreatic ductal adenocarcinoma
with mutated KRAS;
cell lines;
in vitro and in vivo (genetically engineered mouse models) | nd | [37] |
|
| Mutated BRAF inhibitor (vemurafenib) | + | PGC-1α dependent and independent pathways | Mitochondrial-targeted prooxidative drug, elesclomol
-KCN | Melanoma;
cell lines and patient biopsies;
in vitro and in vivo (patient-derived tumor xenograft models)
cell lines | +
+JARID positive slow cycling melanoma |
[19]
[38] |
| + | | Phenformin | Melanoma;
cell lines;
in vitro and in vivo (genetically engineered mouse models) | Delay the onset of acquired resistance to BRAFi | [39] |
| + | PGC-1α dependent mitochondrial biogenesis | Oligomycin A | Melanoma;
cell lines and clinical samples;
in vitro and in vivo (xenograft models) | +JARID positive slow cycling melanoma |
[40, 41] |
| nd | nd | PDK inhibitor (DCA) | Melanoma;
cell lines;
In vitro | nd | [28] |
| nd | nd | Metformin | Melanoma patients; retrospective analysis of clinical records | Not significant | [42] |
|
| Akt inhibitor | nd | nd | Metformin | Acute myeloid leukemia;
cell lines;
in vitro and in vivo (xenograft models) | nd | [22] |
|
Multiple kinase inhibitor
(sorafenib) | nd | nd | PDK inhibitor (DCA) | Hepatocarcinoma; cell lines;
in vitro and in vivo (xenograft models) | + | [25] |
|
