Table 1.
Comprehensive overview of research reports highlighting the antitumor effects induced by PERK targeting.
| Cancer | PERK Function | PERK Targeting Approach | Reported Effect | References |
|---|---|---|---|---|
| Multiple myeloma (MM) | Cytoprotective | mRNA knockdown by siRNAs on MM cell lines cultured in vitro. | Induces autophagy-mediated cell death. | [156] |
| Multiple myeloma (MM) | Cytoprotective | Pharmacological inhibition with compound GSK2606414 in single treatment and combination treatment with Bortezomib (proteasome inhibitor). | Reduces MM cell viability in vitro (induction of apoptosis). Cytotoxic effect of GSK2606414 is additive to that of bortezomib in combination treatments. | [157] |
| Pancreatic cancer; multiple myeloma (MM) | Cytoprotective | Pharmacological inhibition with compound GSK2656157 (derivative of GSK2606414). | Inhibits the growth of human tumor xenograft in mice (decreased angiogenesis; apoptosis induction). Reported side effect of PERK targeting: pancreatic damage (reversible). | [141,158] |
| Pancreatic cancer | Cytoprotective | Pharmacological inhibition with compound GSK2606414. | Inhibits the growth of human tumor xenograft in mice (apoptosis induction). | [159] |
| Breast cancer | Stimulation of cell migration | mRNA knockdown by siRNAs on cell lines cultured in vitro. | Reduces cell migration under hypoxic conditions (transwell and gap closure assays). | [131] |
| Breast cancer | Cytotoxic | Pharmacological activation with compound CCT020312 in combination treatment with taxol. | Combination treatment induces taxol-mediated cell apoptosis and reduces tumor growth of human xenograft in mice. | [160] |
| Breast cancer | Stimulation of cell migration and invasion | Pharmacological inhibition with compound 3-Fluoro-GSK2606414. | Decreases viability in cells undergoing epithelial-to-mesenchymal transition (EMT). Reduces the ability of EMT cells to migrate and to form tumor spheres in vitro. Reduces the metastatic capacity of human tumor cells in mice (xenografts). | [124,161] |
| Breast cancer | Cytotoxic | Pharmacological inhibition with compound HC-5404 | Impairs metastasis by killing quiescent/dormant disseminated cancer cells (DCC) in the MMTV-HER2 mouse model. | [162] |
| Glioblastoma | Stimulation of angiogenesis | mRNA knockdown (shRNAs) | Reduces angiogenesis in vitro (HUVEC cells, tube formation assay). | [163] |
| Colorectal cancer (CRC) | Cytotoxic | Pharmacological activation with compound CCT020312. (CCT) in single treatment and combination treatment with taxol (microtubule stabilizing agent, mitotic blocker) | Promotes apoptosis in vitro. CCT treatment synergistically increases the sensitivity of CRC cells to taxol, both in vitro and in vivo in mouse xenograft models. | [164] |
| Renal carcinoma | Cytoprotective | Pharmacological inhibition with compound 28. | Inhibits the growth of human tumor xenografts in mice. | [165] |
| Renal cell carcinoma (RCC) | Stimulation of angiogenesis | Pharmacological inhibition with compound HC-5404 in single treatment and combination treatment with VEGF receptor tyrosine kinase inhibitors (VEGFR-TKIs) | Single treatment reduces in vivo tumor growth. Combination treatment enhances the antiangiogenic effects of VEGFR-TKIs (human xenografts in mice) by disrupting the adaptive stress response. | [142] |
| Melanoma | Protects cancer cells from paraptosis-induced immunogenicity cell death (ICD) | PERK gene ablation with CRISPR-Cas9 in melanoma cell lines. Pharmacological inhibition with compound AMG44 | PERK gene knockout in melanoma cells and PERK pharmacological inhibition trigger paraptosis and induction of ICD in human xenograft models in mice. | [146] |
| Hepatocellular carcinoma (HCC) | Cytoprotective | Pharmacological inhibition with compound GSK2656157. | Increases proteotoxic stress and reduces cancer cell viability and proliferation in vitro; decreases tumor burden in orthotopic models of HCC in mice. | [166] |