Table 1.
Clinical trials evaluating different therapeutic approaches in patients with TNBC.
| S. No. | Type | Treatment | TNBC patient population | Mechanism of Action | Clinical Phase | Status | References | |
|---|---|---|---|---|---|---|---|---|
| 1. | CHEMOTHERAPY | Paclitaxel | 52 | p53/p21 pathway or Raf-1 kinase activation pathway | II | Completed | (165) | |
| 2. | Nab-paclitaxel | 903 | Inhibit of tumor growth | II/III | Completed | (165, 166) | ||
| 3. | Docetaxel | 127 | Attenuate the effect of BCL-2 and BCL-XL gene | II/III | Completed | (167) | ||
| 4. | Tesetaxel | 674 | PDL-1 Inhibitor | III | Completed | (168) | ||
| 5. | Doxorubicin | 52 | Blocking the topoisomerase 2 | 1/1b | Completed | (169, 170) | ||
| 6. | Epirubicin | 53 | Inhibit totpisomerase II activity | II | Completed | (171) | ||
| 7. | Pegylated liposomal doxorubicin | 39/113 | Blocking the topoisomerase 2 | 1/III | Completed | (172, 173) | ||
| 8. | Cyclophosphamide | 40 | Inhibiting humoral 1 and 2 | II | Completed | (174) | ||
| 9. | Cisplatin | 47 | Inhibit the DNA synthesis | II | Completed | (174, 175) | ||
| 10. | Carboplatin | 647 | Inhibit the DNA synthesis | II | Completed | (176) | ||
| 11. | Eribulin mesylate | 762 | Reversing epithelial-mesenchymal transition to mesenchyal-epethilial transition. | III | Completed | (177) | ||
| 12. | Capecitabine | 434 | Inhibit thymidine monophopshate (ThMP) synthesis | II/III | Recruiting | (178) | ||
| 13. | Gemcitabine | 50 | Activates p38 MAP kinase pathway | II | Completed | NCT02435680; Novartis (Novartis Pharmaceuticals), 2021 | ||
| 14. | Fluorouracil | 647 | Inhibit thymidylate synthesis (TS) | III | Completed | NCT01216111; Zhimin Shao, Fudan University, 2020 | ||
| 15. | Ixabepilone | 91 | Microtubule inhibitor, blocks cell growth by stopping cell division. | – | Recruiting | (179) | ||
| 16. | Taxanes | - | Microtubule inhibitor and inactivate HIF-1α pathway | - | - | (180) | ||
| 1. | RADIOTHERAPY | External beam radiation therapy (EBRT) | - | Radiation to destroy cancer cells | I | Unknown | (163, 164, 181) | |
| 2. | Brachytherapy (149) | - | Limits radiation treatment to the tissue surrounding the lumpectomy | I | Unknown | (163, 164, 181) | ||
| 3 | FLASH-RT | - | Limits the radiation toxicity to the surrounding healthy, normal tissues. | - | - | (182) | ||
| 4 | IMPT | - | Radiotherapy technique to treat tumors in layers of spots at varying depths by altering the number localized proton dose deposition, energy penetration, and magnetic deflection. | - | - | (164) | ||
| 5 | PBT | - | Reduce the needless irradiation of nearby normal tissues and side effects | - | - | (164) | ||
| 1. | ANTIANGIOGENIC THERAPY | Bevacizumab | 54 | Angiogenesis agent by Inhibits the VEGF binding to it cell surface receptor | II | Completed | (183) | |
| 2. | Lenvatinib | 31 | Multiple receptor inhibition VEGFR-1, VEGFR-2, VEGFR-3, FGFR1, FGFR-2, FGFR-3, FGFR-4, PDGFRa, RET and c-KIT. | II | Recruiting | (184) | ||
| 3. | Apatinib | 32 | Inhibits VEGFR-2 receptor reduce tumor vasculature | I | Completed | (185) | ||
| 4. | Cabozantinib | 35 | Inhibits VEGFR-1/2 and -3, TRNKB, FLT-3,KIT,TIE-2, MET,AXL and RET | II | Completed | (186) | ||
| 5. | Anlotinib | 30 | Dual signaling blockade VEGFR2 and MET pathways | I | Unknown | (187) | ||
| 1. | ADJUVANT THERAPY | Accelerated radiotherapy with carbogen and nicotinamide | MDA-MB-231 TNBC xenograft tumors | Radiation with carbogen to destroy cancer cells | 0 | Preclinical | (188) | |
| 2. | Hypothermia | 2 | Heat tissue high as 113 0 F to kill cancer cells | 0 | Unknown | (189) | ||
| 1. | PHOTODYNAMIC THERAPY (PDT) | Protoporphyrin IX | TNBC cell lines (HCC1395, BT-20, MDA-MB-231, and Hs578T) | Inhibits Ras/MEK pathway. | Preclinical | In-vitro | (190) | |
| 1. | IMMUNOTHERAPY | Immune-checkpoint inhibitors (ICI) | Pembrolizumab | 32/84/170 | Inhibit PD-1 pathway. | Ib/II/III | Active | (191–193) |
| 2. | Atezolizumab | 115/41 | Blocking its interaction with PD-1 and B7-1. | I/II | Active | (194) | ||
| 3. | Avelumab | 58 | Blocking its interaction with PD-1 and B7-1. | I | Active | (195) | ||
| 4. | JS001 | 20 | PD-1 Inhibitor | I | Active | (196) | ||
| 5. | Nivolumab | 51 | Blocking interaction with PDL1 and PDL2. | I/II | Active, Not Recruiting | (197) | ||
| 6. | Durvalumab | 45 | Blocking interaction with PDL1 with PD-1 and CD80. | II | Completed | (198) | ||
| 1. | T-Cell Targeted Modulators | Anti-CTLA4 | 35/129 | Inhibit CTLA4 and suppress natural killer cell maturation. | I/II | completed | (199) | |
| 2. | Anti-LAG3 | 363 | Inhibit LAG3 | II | Completed | (200, 201) | ||
| 3. | Anti-TIGIT | - | Inhibit TIGIT | 0 | Not yet | (202) | ||
| 4. | Anti-CD137 agonistic antibody | - | Suppress CD137 receptors. | 0 | Not yet | (203) | ||
| 5. | Anti-OX40 agonistic antibody | - | Suppress OX40 receptors | 0 | Not yet | (203) | ||
| 6. | Anti-CD40agonistic antibody | - | Suppress CD40 receptors | 0 | Not yet | (203) | ||
| 1. | Immunomodulators |
Acetylsalicylic acid |
- |
Disrupts NFkappaB-IL6 signaling axis and inhibits cyclooxygenase (COX) enzyme. |
- | Not yet | (204) | |
| 2. | COX2 inhibitors (indomethacin) | - | Disrupts cancer-cell fibroblast signaling. | - | Not yet | (205) | ||
| 3. | Recombinant IFN-alpha-2b activating. TLR3 receptors |
- | Stimulates JAK-STAT pathway. | - | Not yet | (206) | ||
| 4. | A2AR antagonists | - | Decreases the immunosuppressive mechanisms such as Tregs, CTLA-4, TGF-beta and COX2, eicosanoid mediators. | - | Not yet | (207) | ||
| 5. | CSF-1R inhibitors | - | Target M2 macrophages/TAM | - | Not yet | (208) | ||
| 6. | Anti-TGF-beta antibodies | - | Promotes T cell infiltration. | - | Not yet | (209) | ||
| 7. | L-NMMA (pan-NOS inhibitor) | 15/24 | Increases circulating IL-6 and IL-10 cytokines, in contrast, CD15+ neutrophils and decrease in arginase. | I/II | Recruiting | (210) | ||
| 8. | Oncolytic reoviruses | - | Selectively replicate in cancer cells and then kill them without damaging the healthy cells by enhancing the recruitment of innate immune function and inducing tumor cell apoptosis. | - | Not yet | (211) | ||
| 9. | Anti-IL1beta antibodies | - | Decreases IL-6 production through a transglutaminase 2/NF-κB pathway. | - | Not yet | (212) | ||
| 10. | Poly-ICLC | - | Increase cytokines and immune response. | - | Not yet | (213) | ||
| 11. | Anti-IL-6R antibodies |
- | Decreases the breast cancer cell aggressiveness. | - | Not yet | (214) | ||
| 1. | ADOPTIVE CELL THERAPY (ACT) | EGFR/CD276 | 30 | Induces T cell activation | I | Recruiting | (215) | |
| 2. | ROR1-targeted CAR T cell (LYL 797) | 54 | Harbors synthetic Notch receptors specific for EpCAM or B7-H3 (expressed by ROR1-expressing tumor cells) and reported that these CAR-Ts safely mediated efficient tumoricidal activity without toxicity | I | Recruiting | (215) | ||
| 3. | NKG2DL-targeting CAR-grafted gamma delta (gd) T cells | 10 | Secretes cytokines and chemokines and exhibiting cytotoxicity | I | Recruiting | (215) | ||
| 4. | c-met-RNA CART T cells | 6 | Reduces the proliferation and migration capacity of TNBC | 0 | Recruiting | (215) | ||
| 5. | CART-TnMUC1 cells | 16 | Target antigen-dependent cytotoxicity and released cytokines, chemokines, and granzyme B | I | Recruiting | (215) | ||
| 6. | Anti-meso-CAR vector transduced T cells | 20 | I | Recruiting | (215)) | |||
| 7. | Mesothelin-specific chimeric antigen receptor positive T-cells | 186 | Activate T-cells. | I | Recruiting | (215) | ||
| 8. | PD-1+ TILS | 20 | Inhibition of T cell function and depletion of T cells | i/ii | Recruiting | (102, 215) | ||
| 9. | TC-510 | 115 | Elicits T cell response through mesothelin. | i/ii | Recruiting | (215) | ||
| 1. | CANCER VACCINE (CV) | Dendritic cell vaccine | 23 | Induces the IFN-γ-production by CD4+ T cells. | II | Active/not recruiting | (211) | |
| 2. | AE37 peptide therapeutic vaccine | 29 | Activate CD4+ immune response and stimulate T-helper cells against HER2/Neu expressing cancer cells. | II | Active/not recruiting | (211) | ||
| 3. | Neoantigen personalized DNA vaccine | 18 | Induces the number of neoantigen-specific cytotoxic T cells. | I | Recruiting | (211) | ||
| 4. | PVX-410 | 20 | Induces cytotoxic T lymphocytes (CTLs) to target specific tumor associated antigens such as highly over-expressed tumor antigens XBP1, CD138 and CS1. | II | Recruiting | (211) | ||
| 5. | GP2 | 456 | Activate CD8+ response against the HER2 antigen | II | Completed | (216) | ||
| 6. | Nelipepimut-S | 275 | Stimulate cytotoxic T lymphocytes to lyse of HER2-expressing cancer cells. | II | Completed | (216) | ||
| 7. | Tecemotide | 400 | Stimulate an antigen-specific cellular immune response against MUC1+ cancer cells. | II | Completed | (216) | ||
| 8. | AS/OBI-821 | 349 | Reduces the Tregs, therefore increases the humoral response. | II | Completed | (216) | ||
| 9. | H/K-HELP | 12 | Increases the IFN-γ-production by CD4+ T cells and induces Th1 dependent induces cellular and humoral immune responses. | I | Completed | (216) | ||
| 10 | P10s-PADRE | 24 | Induces the expression of CD16, NKp46 and CD94 expression on NK cells and a serum content of IFN-γ produced by CD4+ T cells. | 1/II | Recruiting | (211) | ||
| 11. | Galinpepimut-S | 90 | Stimulate CD8+ and CD4+ T-cell responses. | II | Recruiting | (211) | ||
| 12. | KRM-19 | 14 | Stimulate cytotoxic T lymphocytes and induces the IFN-γ-production by CD4+ T cells. | II | Completed | (216) | ||
| 13. | Tumor lysate-pulsed DC 23 vaccine | 29/21 | Induces the IFN-γ-production by CD4+ T cells. | II | Completed | (216) | ||
| 14. | RO7198457 (iNEST) | 272 | Enhances anti-tumor activity of atezolizumab (anti–PD-L1) by increasing the number of neoantigen-specific cytotoxic T cells. | II | Active/not recruiting | (211, 217) | ||
| 15. | NANT cancer vaccine (NCV) | 79 | Enhances immunogenic cell death by activating the T cell and NK therapy and also reduces the Tregs | I | Active/not recruiting | (216) | ||
| 16. | Elenagen | 27 | Reduces in the population of suppressive cells in the TME, including regulatory T-cells (Tregs) or myeloid-derived suppressor cells (MDSCs). | I/II | Completed | (216) | ||
| 17. | p53MVA | 11 | Induces the frequencies and persistence of p53-reactive CD8+ T cells. | I | Active/not recruiting | (216) | ||