1. The unfolded protein response: mechanism
1.1. The unfolded protein response pathways
1.2. ER stress-induced apoptosis
2. The unfolded protein response and its effect on tumorigenesis
3. The unfolded protein response and its effect on disease prognosis
4. Therapeutic targeting of unfolded protein response in cancer
Drug | Classification/Mechanism | Development Stage | Disease Indication | Reference |
---|---|---|---|---|
Bortezomib | Proteasome inhibitor | FDA approved | Multiple myeloma, mantle-cell lymphoma | San et al. [97] |
NPI-0052 (salinosporamide A) | Irreversible proteasome inhibitor | Phase I clinical trials | Multiple Myeloma, Advanced malignancies | Chauhan et al. [98] |
Carfilzomib (PR-171) | Selective proteasome inhibitor | Phase I, II, III clinical trials | Multiple Myeloma, Waldenstrom's Macroglobulinemia | |
PS-341 | Selective proteasome inhibitor | Phase II | Multiple Myeloma | Richardson et al. [101] |
CEP-18770 | Proteasome inhibitor | Phase I, II clinical trials and preclinical studies | multiple myeloma, Non- Hodgkin's lymphoma | Piva et al. [102] |
Tanespimycin (17-AAG, (17-Allylamino-17-demethoxygeldanamycin), KOS-953) | HSP90 Inhibitor | Phase I, II, III clinical trials | Gastrointestinal stromal tumors, breast cancer, gynecological, leukemia, lymphoma, melanoma, prostate, renal, thyroid carcinoma, melanoma | |
Alvespimycin (KOS-1022, 17-DMAG) | HSP90 Inhibitor | Phase I clinical trials and preclinical studies | Acute myeloid leukemia, advanced carcinoma | |
Retaspimycin (IPI-504) | HSP90 Inhibitor | Phase II clinical trials | Gastrointestinal stromal tumors, nonsmall cell lung, prostate | Hanson et al. [111] |
PU-H71 | HSP90 Inhibitor | Preclinical studies | Breast cancer, myeloma, myeloproliferative disorder | |
SNX-2112 | HSP-90 inhibitor | Preclinical studies | Gastric cancer | Bachleitner-Hofmann, et al. [114] |
Eeyarestatin I (EerI) | Inhibitor of ER-associated degradation (ERAD) | Preclinical studies | Cross et al. [115] | |
Versipelostatin | GRP78 inhibitor | Preclinical studies | Matsuo et al. [87] | |
(-)-epigallocatechin gallate (EGCG) | GRP78 inhibitor | Preclinical studies | Breast carcinoma | Luo et al. [116] |
Epidermal growth factor (EGF)-SubA | GRP78-targeting cytotoxin | Preclinical murine animal models | Prostate tumor | Backer et al. [90] |
Irestatins | IRE1α inhibitor | Preclinical studies | Multiple Myeloma, | Feldman et al. [117] |
Delta(9)-Tetrahydrocannabinol (THC) | Cannabinoid, activates ER stress and autophagy | Phase I clinical trial | Glioblastoma multiforme | Guzmán et al. [118] |