Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives
Abstract
:1. Introduction
2. Galectin-1
2.1. Thiodigalactoside
2.2. Anginex (β Pep-25)
2.3. OTX008 (0018)
2.4. F8.G7
2.5. GM-CT-01 (DAVANAT®) oraz GR-MD-02
3. Galectin-3
3.1. G3–C12
3.2. Modified Citrus Pectins (MCP)
3.2.1. PectaSol-C
3.2.2. GCS-100
4. Galectin-4
5. Galectin-7
6. Galectin 8
7. Galectin 9
8. Other Galectins
9. Conclusions
Conflicts of Interest
References
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Subtype | Galectins | Model | Structure |
---|---|---|---|
Prototype | 1, 2, 5, 7, 10, 11, 13, 14, 15, 16 | | Each monomer of homodimer contains CRD |
Tandem Repeats | 4, 6, 8, 9, 12 | | Two CRD domains connected with linker |
Chimeric | 3 | | Multimeric structures with one CRD in C terminus and N-terminus. |
Inhibitor | Target | Effect | Refs. |
---|---|---|---|
Thiodigalactoside (TDG) | Melanoma and breast cancer xenografts; Colon and breast cancer xenografts | Induction of apoptosis; Inhibition of angiogenesis, proliferation and tumor growth; Reduction of lung metastases; Restore T cells surveillance | [30,31] |
Anginex (β pep-25) | Ovarian, melanoma and breast cancer xenografts | Inhibition of tumor growth, angiogenesis and migration; Increased sensitivity to radiotherapy and chemotherapy; Synergistic effects with bevacizumab | [33,34,35,36] |
6DBF7; DB16; DB21 | Lung and ovarian cancer and melanoma xenografts | Inhibition of tumor growth; Inhibition of angiogenesis | [37,38] |
OTX008 (0018) | Ovarian cancer xenografts; Head and neck and ovarian cancer cell lines; Clinical trial in patients with advanced solid tumors | Downregulation of cancer cell proliferation; Inhibition of tumor growth, angiogenesis and migration; Synergic effects with chemo- and immunotherapy | [24,39,40,41,42] |
F8.G7 | Endothelial cells; Kaposi’s sarcoma xenografts | Inhibition of tumor growth, angiogenesis, migration | [43,44] |
GM-CT-01 (DAVANAT®) oraz GR-MD-02 | Colon cancer xenografts; Clinical trials in patients with colon cancer and melanoma | Inhibition of tumor growth; Restore the T cells surveillance | [45,46] |
Inhibitor | Target | Effect | Ref. |
---|---|---|---|
G3–C12 | Breast, colon and prostate cancer xenografts | Reduction of lung metastasis; Induction of apoptosis; Inhibition of tumor growth; Synergic effect with chemotherapy | [93,94,95,96] |
Modified citrus pectin (MCP) | Breast and colon cancer xenografts; Prostate cancer cell lines; Patients with advance solid tumors | Inhibition of tumor growth, angiogenesis and metastasis; Induction of apoptosis; Cell cycle arrest; Increase sensitivity to chemotherapy; Rebalance the T cells surveillance | [98,99,100,101,102] |
PectaSol-C Modified citrus pectin | Prostate and ovarian cancer cell lines | Induction of apoptosis; Inhibition of proliferation; Synergic effect with chemotherapy | [98,103,104] |
GCS-100 | Multiple myeloma, DLBCL cell lines; Prostate cancer cell lines; Patients with Chronic lymphocytic leukemia (CLL) | Inhibition of cell growth; Induction of apoptosis; Synergic effect with chemotherapy; Increased sesnsitivity to immunochemotherapy | [92,105,106,107,108,109] |
NCT Number | Inhibitor | Target | Phase | Title of the Study |
---|---|---|---|---|
NCT01723813 | GM-CT-01 | Gal-3 | I/II | Peptide Vaccinations Plus GM-CT-01 in Melanoma |
NCT01724320 | OTX008 | Gal-1 | I | A Phase I, First-in-man Study of OTX008 Given Subcutaneously as a Single Agent to Patients with Advanced Solid Tumors |
NCT02117362 | GR-MD-02 | Gal-3 | I | Galectin Inhibitor (GR-MD-02) and Ipilimumab in Patients with Metastatic Melanoma |
NCT02575404 | GR-MD-02 | Gal-3 | I | GR-MD-02 Plus Pembrolizumab in Melanoma Patients |
NCT01681823 | PectaSol-C | Gal-3 | III | Effect of Modified Citrus Pectin on PSA Kinetics in Biochemical Relapsed PC with Serial Increases in PSA |
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Wdowiak, K.; Francuz, T.; Gallego-Colon, E.; Ruiz-Agamez, N.; Kubeczko, M.; Grochoła, I.; Wojnar, J. Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives. Int. J. Mol. Sci. 2018, 19, 210. https://doi.org/10.3390/ijms19010210
Wdowiak K, Francuz T, Gallego-Colon E, Ruiz-Agamez N, Kubeczko M, Grochoła I, Wojnar J. Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives. International Journal of Molecular Sciences. 2018; 19(1):210. https://doi.org/10.3390/ijms19010210
Chicago/Turabian StyleWdowiak, Kamil, Tomasz Francuz, Enrique Gallego-Colon, Natalia Ruiz-Agamez, Marcin Kubeczko, Iga Grochoła, and Jerzy Wojnar. 2018. "Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives" International Journal of Molecular Sciences 19, no. 1: 210. https://doi.org/10.3390/ijms19010210