Table 1.
Schematic example of inhibitors of RAGE axis with anticancer properties
| RAGE inhibitor/inhibition strategy | Target of inhibition | Cancer type | Effect | Ref. |
|---|---|---|---|---|
| FPS-ZM1 | RAGE | Breast cancer | Reduced cell migration and invasion; decreased tumor growth, metastasis formation and angiogenesis | (260) |
| RAGE | Pancreatic cancer | Reduced tumor growth | (221) | |
| RAGE/HMGB1 | Melanoma | Restoration of anticancer immunity | (205) | |
| RAGE/S100A9 | Colorectal cancer | Restoration of anticancer immunity | (211) | |
| RAGE/S1007 | Breast cancer | Reduced tumor angiogenesis | (99) | |
| RAGE/S1008-A9 | TNBC | Reduced cell proliferation, migration and colony formation | (261) | |
| RAGE/HMGB-1 | Cervical cancer | Reduced LPS-dependent malignant transformation | (262) | |
| RAGE/HMGB-1 | Pancreatic cancer | Reduced tumor growth in combination with gemcitabine | (263) | |
| RAGE/S100P | Nasopharyngeal carcinoma | Reduced cell proliferation and migration | (264) | |
| RAGE/AGEs | TNBC | Reduced cell migration and invasion | (265) | |
| TTP-488 | RAGE/AGEs | Prostate cancer | Reduced tumor formation and cell migration | (174) |
| TTP-488 analogue | RAGE | TNBC | Reduced cell proliferation and survival | (266) |
| RAP | RAGE | Pancreatic cancer and glioma | Reduced tumor growth and metastasis | (267) |
| S100P/RAGE | Pancreatic cancer | Reduced cell proliferation, survival, migration, and invasion | (267) | |
| RAGE | Pancreatic cancer | Delayed tumor development | (152) | |
| RAGE/S100A14 | Esophageal squamous cell carcinoma | Reduced cell proliferation and survival | (268) | |
| RBP | RAGE | Glioblastoma | Reduced tumor growth and angiogenesis | (269) |
| RAGE aptamer | RAGE/S100AB | Colorectal cancer | Reduced tumorigenesis | (270) |
| AGE/RAGE | Melanoma | Reduced tumor growth and liver metastasis | (271) | |
| RAGE | Melanoma | Reduced tumor growth and angiogenesis | (272) | |
| siRNA | RAGE | Breast cancer | Reduced cell proliferation | (273) |
| RAGE/HMGB-1 | Pancreatic cancer | Reduced tumor growth | (161) | |
| RAGE/AGE | Prostate | Reduced cell proliferation | (245) | |
| shRNA | RAGE/HMGB-1 | Breast cancer | Reduced expression of immune checkpoint inhibitors, reduced cell invasion | (274) |
| RAGE/HMGB-1 | Hepatocarcinoma | Reduced cell invasion | (275) | |
| Genetic ablation | RAGE | Hepatocarcinoma | Reduced tumorigenesis | (276) |
| ODNs | RAGE/AGE | Colon cancer | Reduced cell growth, invasion and migration | (277) |
| Primary acute myeloid leukemia | Inhibition of AGE-induced cell growth | (234) | ||
| Neutralizing antibody | RAGE/HMGB-1 | Gastric cancer | Decreased cell survival | (278) |
| RAGE/HMGB-1 | Colorectal | Reduced EMT | (279) | |
| RAGE/AGE | Breast cancer | Reduced cell proliferation | (150, 151) | |
| RAGE/AGE | Colorectal cancer and hepatic | Decreased cell proliferation, migration and invasion | (157, 280) | |
| RAGE/S100A7 | Breast cancer | Reduced cell proliferation, reduced tumor growth and metastasis | (188) | |
| RAGE/sulfated glycosaminoglycans | Lung cancer | Reduced metastasis | (281) | |
| RAGE/HMGB-1 | Thyroid cancer | Reduced expression of the oncogenic cluster mir221/222, implicated in the regulation of cell proliferation | (282) | |
| ADCs | RAGE | Endometrial cancer | Selective cytotoxicity in vitro and in vivo | (283) |
| Pioglitazone | RAGE | Hepatic cancer | Reduced cell proliferation | (284) |
| Chloroquine | RAGE | Pancreatic ductal adenocarcinoma | Reduced tumor growth in vitro and in vivo | (285) |
| BMS-687681 | RAGE | Pancreatic ductal adenocarcinoma | Enhanced efficacy of immunotherapy and radiotherapy | (286) |
| Cromolyn | RAGE/S100P | Pancreatic cancer | Inhibition of tumor growth increased effectiveness of gemcitabine | (287) |
| Papaverine | RAGE/HMGB-1 | Glioblastoma | Reduced cell proliferation and migration | (288) |
| RAGE/HMGB-1 | Fibrosarcoma | Reduced cell proliferation, migration and invasion | (289) | |
| RAGE/HMGB-1 | Glioblastoma | Reduced tumor growth, enhanced radiosensitivity, enhanced efficacy of temozolomide | (290) | |
| Heparin | RAGE/HMGB-1 | Fibrosarcoma | Reduced tumorigenesis and metastasis formation | (291) |
| Quercetin | RAGE/HMGB-1 | Breast cancer | Protection from necrotic insult, induction of apoptosis | (292) |
| Pancreatic cancer | Enhanced gemcitabine effectiveness | (293) | ||
| Metformin | AGE/RAGE interaction | Breast cancer | Reduced expression of angiogenic mediators, reduced cell proliferation | (294) |
| AACOCF3 | RAGE/S100A7 | Breast cancer | Reduced tumor burden and enhanced, immunosuppressive environment | (295) |
| sRAGE | S100A4 | Melanoma | Reduced cell transmigration | (296) |
| HMGB-1 | Glioma | Reduced tumor growth and metastasis formation | (297) | |
| Neutralizing antibody | HMGB-1 | Pancreatic cancer | Reduced tumor growth | |
| Oral cancer | Reduced bone destruction | (161, 298) | ||
| Head and neck cancer | Reduced bone pain associated with bone invasion | (299) | ||
| Colorectal cancer | Reduced tumor growth and metastasis formation | (300) | ||
| Prostate cancer | Sensitization to paclitaxel | (301) | ||
| Ethyl pyruvate | HMGB-1 | Gallbladder cancer | Reduced cell proliferation | (302) |
| Thoracic cancers | Protection from radiation-induced damage | (303) | ||
| Lung cancer | Reduced growth, invasion and migration of nonsmall-cell lung cancer cells | (304) | ||
| Glycyrrhizin | HMGB-1 | Esophageal carcinoma | Reduced tumor growth and angiogenesis | (305) |
| Colorectal cancer | Reduced tumorigenesis and inflammation | (306) | ||
| Invasive breast, lung and cervical cancer | Increased efficacy of anti-PD-1 based immunotherapy | (307) | ||
| Prostate cancer | Sensitization to paclitaxel | (301) | ||
| Gastric cancer | Reduced cell proliferation | (278) | ||
| shRNA | HMGB-1 | Hepatocellular carcinoma | Tumor growth | (308) |
| HMGB-1 | TNBC | Reduced cell viability Reduced EMT transition |
(309) | |
| Neutralizing antibody | S100A4 | Pancreatic cancer | Reduced tumor growth and angiogenesis | (310) |
| Breast cancer | Reduced tumor progression, premetastatic niche formation and T cell infiltration | (311) | ||
| Sulindac | S100A4 | Colon cancer | Reduced metastasis formation | (312) |
| Calcimycin | S100A4 | Colon cancer | Reduced metastasis formation | (313) |
| Peptibody | S100A8/S100A9 | Lymphoma | Reduced tumor growth associated with depletion of MDSCs | (314) |
| Genetic ablation | S100A8/S100A9 | Hepatic cancer | Reduced cell proliferation and tumor growth | (315) |
| Tasquinimod | S100A9 | Prostate cancer | Prolonged survival of patients with metastatic castration–resistant prostate cancer | Clinical trial (316) |
| ONO-2506 | S100B | Glioma | Reduced TAM infiltration increased survival in animal models of glioma | (317) |
| siRNA | S100B | Ovarian cancer | Reduced self-renewal in vitro and tumorigenicity in vivo | (318) |
| Neutralizing antibody | S100B | Colon cancer | Reduced cell proliferation, migration and invasion | (319) |
| Duloxetine | S100B | Glioma | Reduced trafficking of tumor-associated myeloid-derived cells reduced tumor growth | (320) |
| Pentamidine | S100B | Melanoma | Reduced ATP production in ATP chemosensitivity assays | (321) |
| Neutralizing antibody | S100A7 | Colorectal cancer | Reduced cell migration and metastasis formation | (322) |
| Luteolin and quercetin | S100A7 | Squamous carcinoma | Reduced cell migration and invasion | (323) |
| DNA aptamer | S100P | Colon cancer | Reduced cell proliferation, migration and EMT reduced tumor growth | (324) |
| AGEs | Melanoma | Reduced tumor growth | (325) | |
| siRNA | S100P | Nasopharyngeal carcinoma | Reduced cell proliferation, migration and colony formation | (326) |
| PENVE | S100B | Colon cancer | Increased apoptotic rate | (327) |
| Aminoguanidine | Methylglyoxal | Thyroid cancer | Reduced cell migration, invasion and EMT | (328) |
Abbreviations: ADC, antibody drug conjugate; AGE, advanced glycation end product; ATP, adenosine triphosphate; EMT, epithelial mesenchymal transition; HMGB-1, high mobility group box 1; LPS, lipopolysaccharide; MDSC, myeloid derived suppressor cell; ODN, S-oligodeoxynucleotide; PENVE, penthamidine vehiculation; PD-1, programmed cell death protein 1; RAGE, receptor for advanced glycation end products; RAP, RAGE antagonist peptide; RBP, RAGE binding peptide; siRNA, small interfering RNA; shRNA, short hairpin RNA; sRAGE, soluble RAGE; TAM, tumor-associated macrophages; TNBC, triple negative breast cancer.