Table 2.
Therapeutics with clinical potential tested in PyMT.
| Drug name | Target/mechanism of action | Effect | Reference |
|---|---|---|---|
| Immunotherapies | |||
| ANTI-PDL1 | Blocks the Programmed death ligand (PDL1) that is commonly expressed by tumor cells to inhibit T cell activity. | Increased CD8+ T cell activity, decreased tumor burden. | [100] |
| ADIL12– B7-1 | Adenovirus expressing the cytokine IL12 and the co-stimulatory molecule B7-1 that activates T cells. | Complete regression of tumors with no detected relapse. At lower dose, it delayed tumor growth and was still effective. | [110] |
| ANTI-IL4 | Monoclonal antibody against the secreted cytokine IL4. Antibody results in increase M1 macrophages polarization. | No change in tumor onset, latency or burden. But significantly decreased the number of lung metastases. | [90] |
| Drugs targeting DNA or RNA | |||
| EZN-3920 | ErbB3 antisense | Significant reduction in tumor growth and inhibits tumor progression. | [66] |
| Targeted therapies | |||
| GSK-126 | Ezh2 methyltransferase inhibitor | Decrease in hyperplasias and delay in tumor onset. Complete block of metastasis | [42] |
| Buthionine-[S, R]-sulfoximine (BSO) | Inhibitor of GSH (Glutathione) synthesis. | Early treatment increased ROS levels, reduced tumor burden and disrupted progression to later stages. Treatment upon tumor onset did not change ROS levels and had no effect on tumor burden, suggesting a reason why clinical trials have failed. | [108] |
| Anti-MMR nanobody | Nanobody targeting CD206+ TAMs | Specially binds to and label TAMs, allowing for imaging of tumor stroma and hypoxic regions. | [111] |
| Anti-ANG2 antibody (3.19.3) | Blocks ANG2’s ability to bind Tie2, inhibiting an important pro-angiogenic axis | Interfered with angiogenesis, disrupted blood vasculature and inhibits tumor progression | [101] |
| ANTI-CSF1 | Inhibits colony stimulating factor, a macrophage differentiation factor. | Depleted macrophages and delayed tumor regrowth following radiation | [112] |
| PLX3397 | Competitive ATP inhibitor for CSF1 receptor | Eliminated tumor associated macrophages and delayed tumor growth after radiation | [112] |
| DC101 antibody | anti-VEGF | Reduced tumor growth due to impairment of angiogenesis. It also increased the levels of PD-L1, sensitizing tumors for combination with anti-PDL1 antibody. This combination led to significant reduction in tumor burden. | [100] |
| Lapatinib | Tyrosine kinase inhibitor (ErbB2 and EGFR) | Delay tumor growth, | [66] |
| Tamoxifen | Selective estrogen receptor modulator (SERM) that inhibits ER signaling. | Inhibited tumor growth and decreased tumor volume. | [63] |
| Chemotherapy and radiotherapy | |||
| 5 GY focal gamma irradiation from cesium source | Ionizing radiation | Tumor regressed, but regrowth occurs after a period of stasis. | [112] |
| Doxorubicin | Chemotherapy. Inhibits topoisomerase 2, an enzyme important for DNA replication. | Reduced tumor volume due to necrotic cancer cell death. | [113] |