CXCL12-CXCR4/CXCR7 Axis in Colorectal Cancer: Therapeutic Target in Preclinical and Clinical Studies
Abstract
:1. Introduction
2. Cytokines, Chemokines, and Receptors
3. Chemokine CXCL12
4. Chemokine Receptors
4.1. CXCR4
4.2. CXCR7
5. Signaling in CRC Growth, Invasion, and Metastasis
5.1. CXCL12–CXCR4 Axis
5.2. CXCL12-CXCR7 Axis
5.3. CXCR4 and CXCR7 Interactions
6. Therapeutics in Preclinical and Clinical Trials
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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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] |
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Khare, T.; Bissonnette, M.; Khare, S. CXCL12-CXCR4/CXCR7 Axis in Colorectal Cancer: Therapeutic Target in Preclinical and Clinical Studies. Int. J. Mol. Sci. 2021, 22, 7371. https://doi.org/10.3390/ijms22147371
Khare T, Bissonnette M, Khare S. CXCL12-CXCR4/CXCR7 Axis in Colorectal Cancer: Therapeutic Target in Preclinical and Clinical Studies. International Journal of Molecular Sciences. 2021; 22(14):7371. https://doi.org/10.3390/ijms22147371
Chicago/Turabian StyleKhare, Tripti, Marc Bissonnette, and Sharad Khare. 2021. "CXCL12-CXCR4/CXCR7 Axis in Colorectal Cancer: Therapeutic Target in Preclinical and Clinical Studies" International Journal of Molecular Sciences 22, no. 14: 7371. https://doi.org/10.3390/ijms22147371