Table 2.
Potential molecular targets to enhance radiosensitivity of cancer cells.
| Target | Process | Radiosensitization experiments | References |
|---|---|---|---|
| 53BP1 | Involved in DNA repair via the NHEJ and HR pathways. | 53BP1 is knocked down using specific shRNAs in GBM cell lines. | (162) |
| AKT | Involved in cell survival, growth, cancer progression, and DNA damage repair. | Treatment of radioresistant lung cancer cells with Diosmetin, an AKT Pathway Inhibitor. | (163) |
| APE1 | Involved in DNA repair via BER pathway. | Analysis of glioma and pancreas cells lacking APE1. Treatment of radioresistant pancreatic cancer cells with Lucanthone, an APE1 inhibitor. APE1 is knocked down using specific shRNAs in pancreatic cells. |
(47) |
| Artemis | Involved in DNA repair via the NHEJ pathway | Mouse embryonic fibroblasts (MEFs) from DNA-PKcs mutant mice | (164) |
| β1 integrin | Signal transduction | GCS or patient-derived GBM cell cultures treated with AIIB2, a specific antibody against β1 integrin, and JNK inhibitor SP600125. | (165) |
| β-catenin | Wnt/β-catenin pathway | Treatment of radioresistant ESCC with iCRT14, an β-catenin inhibitor. | (74) |
| BRG1 | Chromatin remodeling | BRG1 negative mutant overexpression in colon, breast, and lung cancer cells. Xenograft colon tumors that overexpress the BRG1 negative mutant. |
(71) |
| Catalase | ROS detoxifying | 32D cl 3, a hematopoietic progenitor cell line, was transfected with mt-catalase-plasmid, that overexpressing mitochondrial catalase. Intratracheal injection of mt-catalase plasmid-liposome complexes in C57BL/6NHsd female mice and subsequent thoracic irradiation. |
(126) |
| CHOP (C/EBP homologous protein) | UPR pathway and Autophagy | CHOP is knocked by RNAi in breast cancer cells. | (166) |
| CUX1 | DDR response | CUX1 is knocked by siRNAs in radioresistant breast cancer cells and MEFs (mouse embryonic fibroblasts). | (45) |
| CXCL1 | Inflammation and DNA repair | CXCL1 is knocked by shRNAs in radioresistant GBM cell lines. Xenograft tumors of ESCC cells in combination with CAFs (XRCC1 producing cells) are implanted and after treated with an CXCL1 antibody. |
(27, 58) |
| DNA-PKcs | Involved in DNA repair via the NHEJ pathway | MEFs analysis from DNA-PKcs mutant mice. | (164) |
| EGFR | Cell proliferation and survival | Radioresistant human lung carcinoma cells treated with erlotinib or cetuximab EGFR inhibitors. | (96) |
| EPOR (Erythropoietin Receptor) | Cell cycle arrest and grow | Erythropoietin-induced glioma and cervical cancer cells treated with tyrphostin B42, an inhibitor of JAK2 tyrosine kinase activity. JAK2 is an effector of EPOR. EPOR knockdown in GBM. |
(167, 168) |
| FHIT | DNA methylation | Transfection of oral cancer cells using FHIT-overexpressing cDNA myc-tag plasmid. Generation of radioresistant mouse xenograft tumors that overexpress FHIT |
(169) |
| GADD45α | BER | GADD45α overexpression in X-ray-resistant HeLa cell line, by transfection with GADD45α plasmid. | (48) |
| GAP-43 | Neuronal differentiation | Glioblastoma cells grown under stem conditions (GBMSCs) with a genetic knockdown of GAP-43. | (102) |
| G0S2 (G0/G1 Switch 2) | Lipid metabolism | Targeting G0S2 by shRNAs in GSCs. | (4) |
| GRP78 | ERS endoplasmic reticulum stress | Targeting GRP78 by siRNAs in OPSCC cell lines. GRP78 upregulation with 2-Deoxy-D-Glucose (2-DG) in GSC. |
(13, 116) |
| GSK-3β | Involved in DNA repair via the NHEJ and HR pathways. | Inhibition of GSK-3β in pancreatic cancer cells using LiCl, AR-A014418, or SB216763 GSK inhibitors. Targeting GSK-3β by siRNAs in pancreatic cancer cell lines. |
(170, 171) |
| HDAC | Histone deacetylase | Inhibition of HDAC in human prostate cancer cell lines using suberoylanilide hydroxamic acid (SAHA). Inhibition of HDAC in radioresistant esophageal carcinoma cells lines using trichostatin A and sodium butyrate. |
(172, 173) |
| HDAC6 | Histone deacetylase | Inhibition of HDAC6 in radioresistant GSC using HDAC6i. | (174) |
| JNK (c-Jun N-terminal kinase) | UPR pathway and apoptosis | Inhibition of JNK in radioresistant breast cancer cell lines using SP600125. | (166) |
| KDMs containing a Jumomji C (JmjC) domain | DNA methylation | Inhibition of KDM in radioresistant lung cancer cell lines using JIB-04. | (175) |
| KLC4 | Mitochondrial homeostasis | Targeting KLC4 by siRNAs in lung cancer cell lines. Generation of mouse xenograft tumors with lung cancer cells lacking KLC4. |
(135) |
| Ku70 | Involved in DNA repair via the NHEJ pathway | Ku70 negative mutant overexpression in embryonic stem cells. | (176) |
| LIG4 | Involved in DNA repair via the NHEJ pathway | Inhibition of LIG4 in colorectal cancer cells using SCR7 inhibitor. Targeting LIG4 by shRNAs in colorectal cancer cell lines. |
(55) |
| LOXL2 | EMT phenotype | LOXL2 knockdown by shRNA in castration-resistant prostate cancer cells. | (155) |
| MGMT | DNA-methyltransferase | Targeting MGMT by siRNAs in breast cancer cells lines. | (177) |
| MnSOD | ROS detoxifying | Targeting MnSOD by siRNAs in human pancreatic cancer cell lines. Intratracheal injection of MnSOD-PL plasmid-liposome complexes (that overexpress MnSOD) in C57BL/6NHsd female mice and subsequent thoracic irradiation. |
(126, 138) |
| MSI1 | Involved in DNA repair via the HR pathway | Silencing of MSI1 by shRNA in MSI1-high-expressing radioresistant GBM cell line. Generation of mouse xenograft tumors with GMB cancer cells lacking MSI1. |
(67) |
| NFBD1 | Involved in DNA repair via the HR pathway | Silencing of NFBD1 by shRNA in radioresistant NPC cell line. | (65) |
| OGG1 | Involved in DNA repair via the BER pathway | Silencing of OGG1 by siRNAs in CRC cell lines. Inhibition of OGG1 in CRC cell lines using Chembridge 5245457 and 5552704 inhibitors. |
(46) |
| P53 | Transcription | Transfection of NSCLC cells using p53-overexpressing pCDNA3.1-p53 plasmid. | (178, 179) |
| PARP-1 | Involved in DNA repair via the BER pathway | Inhibition of PARP-1 in HPV- negative in OPSCC using Olaparib. | (43) |
| PDK1 | Signal transduction | PDK1 inhibition by siRNAs in hepatocellular carcinoma (HCC). PDK1 inhibition by BX795 in HCC. |
(157) |
| PERK | Endoplasmic reticulum stress | Silencing of PERK by siRNAs in OPCC cell lines. | (110) |
| PI3k/mTOR | Signaling pathway | Dual PI3K/mTOR inhibition with BEZ235 in patient-derived OSCC cells or prostate cancer cell lines. Treatment of OSCC cell lines with RAD001 inhibitor decreases the phosphorylation and activation of mTOR and increases the RR. |
(50, 84) |
| PNKP (Polynucleotide Kinase 3’-Phosphatase) | Involved in DNA repair via the NHEJ pathway | Inhibition of PNKP in prostate adenocarcinoma cancer cell lines using A12B4C3 PNKP inhibitor. | (180) |
| Pol β | Involved in DNA repair via the BER pathway | Human adenocarcinoma cells or MEFs cell lines that grow in conditions of confluence and expressing a dominant negative of Pol β. | (181–183) |
| Rad51 | Involved in DNA repair via the HR pathway | Cells treated with chronic hypoxia had a reduced RR. Knocking down Rad51 with siRNA to levels like the levels seen under chronic hypoxia also radiosensitizes human lung cancer cells. | (184) |
| RPA1 | Involved in DNA repair via the HR pathway | Targeting RPA1 by shRNAs in radioresistant hypopharyngeal cancer cell. | (64) |
| SHP1 | Cell cycle regulation | Targeting SHP1 by siRNAs in radioresistant NSCLC cells. | (86) |
| SOCS | Signal transduction | Ectopic expression of SOCS1 in GBM cells. Blocking SOCS3 expression (by expressing a dominant-negative STAT3) in GBM cells. |
(185) |
| TGF-β receptor | Signal transduction | Inhibition of TGF-β receptor in radioresistant gastric cancer cells using LY2109761. | (186) |
| Topo II α (DNA Topoisomerase II α) | Replication and transcription | Treatment of radioresistant laryngeal squamous cancer cells with 5-aza-2’-deoxycytidine, a DNA methyltransferase inhibitor. | (187) |
| WISP1 | EMT | ESCC KYSE-150R cell line was treated with WISP1-specific neutralizing antibody. | (148) |
| WntT7 | Signal transduction | Overexpression of Wnt7a in NSCLC by pcDNA6-Wnt7a transfection. | (188) |