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Table 4. Summary of preclinical studies with “first-generation” SINEs in human solid tumors
Tumor type Preclinical SINE(s) Cellular effects Remarks Ref.
model(s)
Renal cancer In vitro/xenograft KPT-185, KPT-251 Growth inhibition, apoptosis, SINEs compare favorably to sorafenib [95]
cell cycle arrest
In vitro/xenograft Selinexor Growth inhibition, apoptosis [158]
Prostate cancer In vitro/xenograft Selinexor Reduced proliferation, apoptosis SINEs synergize with doxorubicin [159]
KPT-185, KPT-251 (no cell cycle arrest)
In vitro/xenograft Selinexor, KPT-251 SINEs reduce bone metastasis [160]
In vitro/xenograft Selinexor, KPT-251 Growth inhibition, apoptosis, SINEs sensitize cells to docetaxel [161]
increased DNA damage
Breast cancer In vitro/xenograft Selinexor, KPT-185, Growth inhibition, apoptosis Mechanism related to STAT3 and survivin [162]
KPT-251, KPT-276
In vitro/xenograft Selinexor Restores sensitivity to tamoxifen [163]
In vitro/xenograft Selinexor Growth inhibition Effective as single agent and synergizes [164]
with chemotherapy in triple-negative BC
Ovarian cancer In vitro Selinexor, KPT-185 Apoptosis SINEs synergize with chemotherapy. [165]
Mechanism related to IGF2BP1
In vitro/xenograft Selinexor, KPT-185 Apoptosis (p53-dependent and Overcomes resistance to platinum com- [166]
p53-independent) pounds
In vitro Selinexor Reduced proliferation, apoptosis Synergizes with cisplatin. Mechanism re- [167]
lated to FoxO1
Colorectal cancer In vitro/xenograft Selinexor Reduced proliferation, apoptosis Synergizes with radiotherapy [168]
Liver cancer In vitro/xenograft Selinexor Growth inhibition, apoptosis cell [169]
cycle arrest
Pancreatic cancer In vitro/xenograft KPT-185, KPT-127, Reduced proliferation, apoptosis Mechanism related to PAR-4 [170]
KPT-205, KPT-227
In vitro/xenograft KPT-185 Reduced proliferation and mi- Mechanism related to Fbw7 and Notch-1 [171]
gration, apoptosis
In vitro/xenograft Selinexor Growth inhibition, apoptosis Synergizes with gemcitabine [172]
In vitro Selinexor Reduced proliferation and mi- Mechanism related to miR-145 micro RNA [173]
gration
Non-small cell lung In vitro/xenograft Selinexor Reduced proliferation, apopto- Synergizes with cisplatin. Effective against [174]
cancer sis, cell cycle arrest NSCLC cells with different molecular al-
terations
In vitro/xenograft KPT-185, KPT-276 Reduced viability, apoptosis, cell KPT-185 active against NSCLC cell lines [175]
cycle arrest resistant to EGFR-TKIs
In vitro/xenograft Selinexor, KPT-185 Synthetic-lethal interaction with K-Ras. [176]
Mechanism related to NF-κB pathway
Thyroid cancer In vitro/xenograft Selinexor Growth inhibition, apoptosis, Synergizes with doxorubicin [177]
cell cycle arrest
Thymic epitelial In vitro/xenograft Selinexor Reduced proliferation, apoptosis p53-dependent and independent effect [89]
tumors
Sarcoma In vitro/xenograft Selinexor Growth inhibition, apoptosis, Study on liposarcoma [178]
cell cycle arrest
In vitro/xenograft Selinexor Growth inhibition, apoptosis Synergizes with proteasome inhibitors. [179]
Mechanism related to NF-κB pathway
In vitro/xenograft Selinexor Cell cycle arrest Activity against a wide variety of sarcoma [180]
models including liposarcoma and gastro-
intestinal stromal tumor
In vitro/xenograft Selinexor Growth inhibition, apoptosis Marfilzomib increases sensitivity to Se- [181]
linexor. Mechanism related to NF-κB path-
way and survivin
In vitro/xenograft Selinexor Growth inhibition, apoptosis, Study on Ewing sarcoma. Synergizes with [97]
cell-cycle arrest the IGF-1R inhibitor linsitinib
Mesothelioma In vitro/xenograft Selinexor, KPT-251, Growth inhibition, apoptosis, SINEs synergize with survivin inhibitor [182]
KPT-276 cell-cycle arrest YM155
Glioma Patient-derived Selinexor, KPT-251, Growth inhibition, apoptosis [183]
cells/xenograft KPT-276
In vitro/xenograft Selinexor Enhances radiosensitivity of glioblastoma [184]
cells
Melanoma In vitro/xenograft Selinexor, KPT-185, Growth inhibition, apoptosis, SINEs synergize with BRAF inhibitors. In- [185]
KPT-251, KPT-276 cell cycle arrest dependent of BRAF mutational status
In vitro/xenograft Selinexor, KPT-276 Growth inhibition, apoptosis Independent of BRAF mutational status [186]
Multiple types In vitro Selinexor DNA damage (double-strand Synergizes with DNA-damaging agents [187]
(solid) breaks)
Pediatric cancer In vitro/xenograft Selinexor Activity against a broad range of pediatric [188]
(solid and cancer types. Independent of TP53 muta-
hematological) tion status