Table 1.
Modulators of CXCL12–CXCR4/CXCR7 axis in preclinical and clinical studies of gastrointestinal cancers.
| Inhibitor/Antagonist | Target | Cell-Line/Disease | Biological Effect Monitored/Clinical Trial Number | Trial Phase | References |
|---|---|---|---|---|---|
| Preclinical Studies: | |||||
| CCX754 and CCX771 | CXCR7 | Murine C26 colon carcinoma | 40% Reduction in lung metastases/NS effect in Liver | [103] | |
| Human HT29 colorectal adenocarcinoma | 50% Reduction in lung metastases/NS effect in Liver | [103] | |||
| LY2510924 | CXCR4 | Colorectal carcinoma | Inhibition of tumor growth | [120] | |
| CTCE-9908 | CXCR4 | Esophageal cancer | Reduction in metastatic spread and primary tumor growth | [122] | |
| TN14003 | CXCR4 | Pancreatic cancer | Inhibition of migration and invasion | [123] | |
| Plerixafor (AMD3100) | CXCR4 | AGS and kato III Gastric Cancer (GC) Cell lines |
Inhibition of GC cell invasion | [124] | |
| AMD3100 | CXCR4 | BGC-823, and SGC-7901 human GC cell lines | Enhances docetaxel cytotoxicity in vitro | [125] | |
| MSX-122 | CXCR4 | Apc+/Min mice | Blocked EGFR transactivation by CXCL12 and reduced tumor burden | [126] | |
|
Clinical
Studies: |
|||||
| AMD3100 (+Cemiplimab) |
CXCR4 | Metastatic pancreatic cancer | NCT04177810 | Recruiting | ClinicalTrials.gov |
| AMD3100 | CXCR4 | Pancreatic cancer | NCT02695966 | Completed Phase1 |
ClinicalTrials.gov |
| AMD3100 | CXCR4 | Colorectal, Pancreatic cancer | NCT03277209 | Terminated phase1 | ClinicalTrials.gov |
| AMD3100 | CXCR4 | Colorectal, Pancreatic cancer | NCT02179970 | Completed Phase1 | ClinicalTrials.gov |
| MSX-122 | CXCR4 | Refractory metastatic or Locally advanced solid tumors | NCT00591682 | Suspended Phase1 | ClinicalTrials.gov |
| Motixafortide (BL-8040), (+Pembrolizumab), Chemotherapy of Onivyde |
CXCR4 | Metastatic pancreatic adenocarcinoma |
NCT02826486 | Active Phase 2a |
[127] ClinicalTrials.gov |
| BL-8040 or BKT140, Multiple immunotherapy-based treatment combinations | CXCR4 | Metastatic pancreatic ductal adenocarcinoma | NCT03193190 | Recruiting (Phase1b/2) |
ClinicalTrials.gov |
| BL-8040 or BKT140, Multiple immunotherapy-based treatment combinations | CXCR4 | Metastatic gastric and esophageal cancer | NCT03281369 | Recruiting Phase1b/2 |
ClinicalTrials.gov |
| BL-8040 or BKT140 (+Pembrolizumab) |
CXCR4 | Metastatic pancreatic cancer |
NCT02907099 | Active Phase2b |
ClinicalTrials.gov |
| BL-8040 (+Cemiplimab) |
CXCR4 | Pancreatic cancer | NCT04543071 | Recruiting Phase 2 |
ClinicalTrials.gov |
| Olaptesed pegol (NOX-A12) alone or(+Pembrolizumab) | CXCL12 | Colorectal and pancreatic cancer | NCT03168139 | Completed Phase1/2 |
[128] ClinicalTrials.gov |
| LY2510924 | CXCR4 | Colorectal and pancreatic cancer | Dose escalation and dose confirmation | Phase1 | [121] |