Table 1.
Pre-clinical studies of CXCL12-CXCR4/CXCR7 signaling axis inhibitors/antagonists in tumors
| Inhibitor/ Antagonist | Target | Cancer | Model | Effects | References |
|---|---|---|---|---|---|
| AMD3100 (+CA4-NPs) | CXCR4 | Breast cancer | Mouse model of metastatic orthotopic 4T1 breast cancer | Tumor growth and metastasis were significantly reduced. | 134 |
| A delivery system by modifying paclitaxel-loaded PEGylation bovine serum albumin nanoparticles with AMD3100 | CXCR4 | Ovarian cancer | Xenograft mouse model of ovarian cancer cell line Caov3 cells | The number of metastatic lesions in mice was reduced. | 137 |
| AMD3465 (+D1MT) | CXCR4 | Breast cancer | Mouse model of metastatic 4T1 breast cancer | It slowed bone metastasis and significantly prolonged survival in breast cancer mice. | 123 |
| AMD3465 | CXCR4 | Bladder cancer | Bladder cancer cell lines SW780 | It inhibited the proliferation and migration of bladder cancer cells through CXCL12/CXCR4/β-Catenin axis. | 124 |
| AMD11070 | CXCR4 | Melanoma | Melanoma cell lines CHL-1 and A375 | It inhibited melanoma cell migration. | 125 |
| AMD11070 | CXCR4 | Oral cancer | Oral cancer cell inoculation induced mouse model | It inhibited lung metastasis of oral cancer cells in mice. | 126 |
| MSX-122 | CXCR4 | Breast cancer, squamous cell carcinoma of the head and neck, and uveal melanoma | MDA-MB-231 breast cancer cell induced breast cancer mice, 686LN Ms cell injection induced cervical cancer mice, overexpression of HGF/TGF- β / CXCR4/MMP2 oelanoma OMM2.3 cells induced uveal melanoma micrometastasis mice | MSX-122 blocked cancer metastasis in mice. | 127 |
| CTCE-9908 | CXCR4 | Prostate cancer | Xenograft mouse model of prostate cancer cells | CTCE-9908 resulted in a decrement of tumor weight by about 20%. | 128 |
| BKT140 | CXCR4 | AML | Blasts of AML | It mediated AML cells apoptosis through Akt / ERK pathway. | 144 |
| Peptide R (+ anti-PD-1) | CXCR4 | Colon cancer and melanoma | MC38 colon cancer and B16 melanoma-human CXCR4 transduction homologous mouse models | Tumor growth were reduced. | 149 |
| PL-peptide R | CXCR4 | Melanoma | Melanoma B16-CXCR4 C57BL / 6 mice | It reduced lung metastasis and increased survival in melanoma mice. | 150 |
| Synthetic peptide E5 | CXCR4 | Breast cancer | Mouse model of breast cancer inoculated subcutaneously with 4T1 cells | It enhanced the efficacy of a variety of chemotherapy agents | 151 |
| M-E5 | CXCR4 | AML | Splenocyte of primary leukemia induced AML mouse model | M-E5 significantly prolonged the survival time of AML mice. | 152 |
| TF14016 | CXCR4 | Small cell lung cancer | Severe combined immunodeficiency mice inoculated with small cell lung cancer cells | It significantly inhibited the size and number of lung metastases. | 140 |
| Ulocuplumab | CXCR4 | Rhabdomyosarcoma | RH30 alveolar rhabdomyosarcoma cell line | It reduced the migration and invasion of RH30 alveolar rhabdomyosarcoma cell line. | 154 |
| Ulocuplumab (+activated and expanded natural killer cells) | CXCR4 | Rhabdomyosarcoma | Immunodeficient NSG mouse model implanted with CXCR4 RH30 cells | This therapy inhibited the invasion and metastasis of rhabdomyosarcoma cells. | 154 |
| PF-06747143 (+bortezomib) | CXCR4 | MM | Mouse model of disseminated MM | The combination therapy reduced the burden of bone marrow tumors. | 158 |
| LY2624587 | CXCR4 | Hematological malignancies | Mouse xenograft models developed from human leukemia and lymphoma cells expressing high levels of CXCR4 | It induced dose-dependent cell death in human hematological cancer cells. | 159 |
| CCX754 or CCX771 | CXCR7 | Colorectal cancer | Human HT29 colorectal cancer cells inoculation induced mouse model | Treatment with CCX754 or CCX771 reduced tumor growth. | 161 |
| Nanobodies (such as NB1 and NB3) | CXCR7 | Head and Neck Cancer | Head and neck cancer cells (22A) | It reduced the secretion of angiogenic factors in head and neck cancer cell lines | 162 |
| X7Ab (+temozolomide) | CXCR7 | Glioblastoma | Orthotopic xenograft of human glioblastoma in mice with severe combined immunodeficiency | Combination therapy prolonged the survival time of glioblastoma mice | 163 |
| NOX-A12 (+radiotherapy) | CXCL12 | Brain tumor | N-ethyl-N-nitrosourea induced rat model of brain tumor | Combined treatment slowed down tumor growth and prolonged the survival time of model animals | 171 |
| MiR-9 | CXCR4 | Oral squamous cell carcinoma | Oral squamous cell carcinoma cell lines | MiR-9 reduced the oral squamous cell carcinoma proliferation. | 172 |
| CXCL14 | CXCR4 | — | THP-1, Jurkat (human T cell leukemia derived cell line), and BaF/3 (mouse pre-B cell line) cells | It inhibited CXCL12-mediated chemotaxis and migration of human bone marrow-derived hematopoietic progenitor cells and leukemia-derived cells. | 173 |
| Zerumbone | CXCR4 | Breast cancer and pancreatic cancer | Breast cancer cell lines and pancreatic cancer AsPC-1 cells | It reduced CXCR4 expression in breast cancer and inhibited invasion of breast cancer and pancreatic cancer. | 174 |
| OBW | CXCR4 | Colon cancer | The immortalized human colon cancer HCT116 | OBW abolished CXCL12-induced invasion of colon cancer cells | 175 |