Table 3.
Advances in hypoxia-related chemotherapy targeting GSC.
| Chemo Agent | Function | Reference |
|---|---|---|
| TMZ | associates with HIF-1α and prolong survival span of GBM patients | (Lo Dico et al., 2018 [120]; Struve et al., 2020 [117]) |
| TMZ plus EGFRvIII | EGFRvIII enhances hypoxia-induced death and cooperates with TMZ to prolong survival of patients with MGMT promoter methylated GBM | (Struve et al., 2020 [117]; Luger et al., 2020 [121]) |
| TMZ plus SNAP | SNAP induces HIF-1α and cooperates with TMZ to benefit survival span of GBM patients with MGMT promoter methylated | (Tsai et al., 2019 [122]) |
| TMZ plus metformin | reverts chemoresistance of GBM during hypoxia via inhibition of PI3K/mTOR pathway | (Lo Dico et al., 2019 [120]) |
| Biweekly TMZ plus bevacizumab | well tolerated by refractory GBM patients but increases regional hypoxia | (Badruddoja et al., 2017 [123]; Gerstner et al., 2020 [124]) |
| TMZ plus Decitabine | increases cytotoxicity of HIF-1α-related chemo-agent | (Gallitto et al., 2020 [127]) |
| TMZ plus imipramine | reduces cytotoxic effect of TMZ under hypoxia | (Bielecka and Obuchowicz, 2017 [126]) |
| TMZ plus tranylcypromine | reduces cytotoxic effect of TMZ under hypoxia | (Bielecka and Obuchowicz, 2017 [126]) |
| N45 | inhibits proliferation through hypoxia-associated ROS/PI3K/Akt pathway in TMZ-resistant GBM | (Zhang et al., 2020 [128]) |
| Tacrolimus (FK506) | reduce GBM tumor volume and hypoxia-induce surface markers (ki67, GFAP and nestin) in GSC | (Torres et al., 2018 [119]) |
| UDCA bortezomib plus BTZ | stabilizes expression of HIF-1α and a promising therapy for GBM patients | (Yao et al., 2020 [130]) |
| BAL101553 | targets hypoxia-mediated angiogenesis of GBM | (Bergès et al., 2020 [131]) |
| Bevacizumab plus carmustine | not enhance incidence of hematologic toxicity but attributes to regional hypoxia in recurrent GBM | (Yerram et al., 2019 [132]) |
| nimotuzumab | an anti-EGFR antibody that upregulates survival span of GBM patients | (Ronellenfitsch et al., 2018 [135]) |
| Evofosfamide plus bevacizumab | activated during hypoxia and well tolerated by bevacizumab-regressive GBM patients | (Brenner et al., 2018 [133]; Takakusagi et al., 2018 [134]) |
| amitriptyline | stimulates phenotypical switch from GSCs to non-GSCs | (Bielecka-Wajdman et al., 2017 [125]) |
| digoxin | inhibits HIF-1α and HIF-2α to target GBM | (Patocka et al., 2020 [136]) |
| digitoxin | suppresses HIF-1α to target GSCs | (Lee et al., 2017 [137]) |
| Cetuximab | reduces translation of HIF-1α to target GBM | (Ferreira et al., 2020 [138]) |
| Topotecan | reduces translation of HIF-1α to target GBM | (Bernstock et al., 2017 [139]) |