TABLE 2.
Different categories of inhibitors that target stimuli and signaling pathways associated with EMT and are targeted in current clinical trials.
| Target class | Functional class | Drug Name | Cancer type | Clinical status (first posted) |
| Inhibitors of extracellular mediators and their corresponding receptors | ||||
| TGF-β–TGF-β receptor inhibitors | TGF-β receptor inhibitor | TEW-7197 | Urothelial Carcinoma Recurrent, Advanced Urothelial Carcinoma, Myelodysplastic Syndromes | NCT04064190(2019); NCT03074006(2017) |
| TGFβ receptor ectodomain-IgG Fc fusion protein | AVID200 | refractory advanced and metastatic malignancies, Myelofibrosis (Myeloproliferative Neoplasms Research Consortium [MPN-RC] 118) | NCT03834662(2019); NCT03895112(2019) | |
| a bifunctional fusion protein targeting PD-L1 and TGF-β | MSB0011359C (M7824) | Stage II-III HER2 Positive Breast Cancer, Locally Advanced or Metastatic Second Line (2L) Biliary Tract Cancer (Cholangiocarcinoma and Gallbladder Cancer), Solid Tumors, Recurrent Respiratory Papillomatosis, HPV Associated Malignancies | NCT03620201(2018); NCT03833661(2019); NCT02699515(2016); NCT02517398(2015); NCT03707587(2018); NCT03427411(2018) | |
| CAR-T cells that target GPC3 (GPC3-CART cell) and/or soluble TGFβ (GPC3/TGFβ-CART) | GPC3-T2-CAR-T | Hepatocellular Carcinoma, Squamous Cell Lung Cancer | NCT03198546(2017) | |
| IL-6/IL-6R inhibitors | Monoclonal antibody | Siltuximab (CNTO-328, Tocilizumab) | Metastatic Pancreatic Cancer; multiple myeloma (MM) and systemic AL amyloidosis (AL) | NCT04191421(2019); NCT03315026(2017) |
| EGF/EGFR inhibitors | Tyrosine kinase inhibitor | Afatinib (BIBW2992) | Chordoma, | NCT03083678(2018) |
| Dacomitinib (PF00299804) | EGFR Mutant Lung Cancer | NCT03755102(2018) | ||
| Osimertinib | Stage I-IIIA EGFR-mutant Non-small Cell Lung Cancer, stage IIIB-IV or Recurrent Non-small Cell Lung Cancer | NCT03586453(2018); NCT03434418(2018); NCT03433469(2018); NCT03191149(2018) | ||
| Brigatinib (AP26113) | Advanced Non-small Cell Lung Cancer (NSCLC), Anaplastic Large Cell Lymphoma, Advanced Malignant Neoplasm | NCT02737501(2016); NCT02706626(2017); NCT03719898(2018); NCT03868423(2019); NCT03707938(2018); NCT03596866(2019); | ||
| inhibitor for (EGFR, HER2, and ErbB4) | Poziotinib (HM781-36B) | EGFR Exon 20 Mutant Advanced NSCLC, Breast Cancer, Stage IV Lung Adenocarcinoma with HER2 Mutation | NCT03066206(2017); NCT03066206(2017); NCT03744715(2018); NCT03318939(2017); NCT02979821(2016) | |
| Monoclonal antibody | Panitumumab | Anaplastic Lymphoma Kinase-Positive (ALK +), Advanced Non-Small-Cell Lung Cancer (NSCLC) | NCT03535740(2019) | |
| HLX07 | Advanced Solid Cancers | NCT02648490(2016) | ||
| PDGF/PDGFR inhibitors | Tyrosine kinase inhibitor | Axitinib | Pheochromocytoma, Paraganglioma, Renal Cell Carcinoma, Hepatobiliary Neoplasm, Liver Neoplasm, Biliary Tract Neoplasms, Cervical Cancer, Non-Small Cell Lung Cancer, Urothelial Cancer | NCT03839498(2019); NCT03494816(2018); NCT04010071(2019); NCT03826589(2019); NCT03472560(2018); NCT03341845(2017) |
| FGF/FGFR inhibitors | Tyrosine kinase inhibitor | Lenvatinib | Advanced Biliary Tract Cancer, Thyroid Neoplasms, Advanced Gastric Cancer, Non-small Cell Lung Cancer, Solid Tumor, Thyroid Cancer | NCT04211168(2019); NCT03573960(2018); NCT03609359(2018); NCT03829332(2019); NCT03009292(2017); NCT03139747(2017) |
| Nintedanib (BIBF1120) | Appendix Cancer, Lymphangioleiomyomatosis, Adenocarcinoma of the Lung | NCT03287947(2017); NCT03062943(2017); NCT04046614(2019) | ||
| Pazopanib | Refractory Solid Tumors, Metastatic Sarcoma, Recurrent Sarcoma, Resectable Sarcoma, Advanced Renal Cell Carcinoma Metastatic Renal Cell Carcinoma | NCT02691767(2016); NCT04199026(2019); NCT03200717(2017) | ||
| Ponatinib | Medullary Thyroid Cancer, Acute Myeloid Leukemia, Accelerated Phase Chronic Myeloid Leukemia, Blast Phase Chronic Myeloid Leukemia, GIST, Malignant, Chronic Myeloid Leukemia, Acute Lymphoblastic Leukemia, Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia | NCT03838692(2019); NCT03934372(2019); NCT03171389(2017); NCT04233346(2020); NCT03709017(2018) | ||
| TNFα inhbitors | Monoclonal antibody | Infliximab | Advanced Melanoma | NCT03293784(2017) |
| Hedgehog/Smoothened inhibitors | Smoothened antagonists (small-molecule inhibitor) | Vismodegib | Stomach Neoplasms, Basal Cell Carcinoma, Metastatic Basal Cell Carcinoma, Locally Advanced Basal Cell Carcinoma, Advanced Solid Tumors | NCT03052478(2017); NCT03035188(2017); NCT03610022(2018); NCT03297606(2017) |
| Sonidegib | Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Basal Cell Carcinoma | NCT04007744(2019); NCT04066504(2019) | ||
| Notch/Notch ligand (Delta-like and Jagged) inhibitors | Small-molecule inhibitor | γ-secretase inhibitor: LY3039478 | Advanced Solid Tumor | NCT02836600(2016) |
| γ-secretase inhibitor: PF-03084014 | Desmoid Tumor, Aggressive Fibromatosis, Desmoid-Type Fibromatosis, Recurrent Desmoid-Type Fibromatosis, Unresectable Desmoid-Type Fibromatosis | NCT03785964(2018); NCT04195399(2019) | ||
| PAN-Notch inhibitor BMS-906024 | recurrent or metastatic Adenoid Cystic Carcinoma | NCT03691207(2018) | ||
| WNT/Frizzled inhibitors | Wnt5a mimetic | Foxy-5 | Colon Cancer | NCT03883802(2019) |
| Peptidomimetics | CWP232291 | Acute Myeloid Leukemia | NCT03055286(2017) | |
| Inhibits the recruiting of β-catenin with its co-activator CBP | PRI-724 | Liver Cirrhosis | NCT03620474(2018) | |
| Inhibitors of intracellular signaling pathways | ||||
| SRC inhibitors | Tyrosine Kinase inhibitor | Dasatinib (BMS-354825) | Relapsed AML, Waldenstrom Macroglobulinemia, Relapsed CML | NCT03560908(2018); NCT04115059(2019); NCT03573596(2018) |
| Bosutinib (SKI-606) | Metastatic Breast Cancer, Chronic Myeloid Leukemia, Advanced Solid Tumors | NCT03854903(2019); NCT02810990(2016); NCT03297606(2017) | ||
| FAK inhibitors | Tyrosine Kinase inhibitor | Defactinib (VS-6063) | Malignant Pleural Mesothelioma, Advanced Solid Tumors | NCT04201145(2019); NCT02546531(2015) |
| PI3K/AKT/mTOR inhibitors | PI3K inhibitor | Idelalisib | Follicular Non-Hodgkin’s Lymphoma Refractory, Relapsed Diffuse Large B-cell Lymphoma, B-cell Lymphoma Recurrent, B-cell Chronic Lymphocytic Leukemia | NCT03568929(2018); NCT03576443(2018); NCT03757000(2018) |
| AKT inhibitor | AZD5363 | Advanced Solid Tumors, Advanced Breast Cancer | NCT03310541(2017); NCT03182634(2017) | |
| Temsirolimus | Non-muscle Invasive Bladder Cancer, | NCT02753309(2016) | ||
| Tyrosine kinase inhibitor | CX-4945 | Recurrent Medulloblastoma | NCT03904862(2019) | |
| AURKA/SYK | Tyrosine kinase inhibitor | Midostaurin | Acute Myeloid Leukemia, AML/MDS | NCT03951961(2019); NCT04097470(2019) |
| AXL inhibitors | Tyrosine Kinase inhibitor | BGB324 | Recurrent Glioblastoma Undergoing Surgery, Advanced NSCLC | NCT03965494(2019); NCT03184571(2017) |
| RAS/RAF/MAPK inhibitors | RAF inhibitor | Sorafenib | Recurrent or Metastatic Triple Negative Breast Cancer, Advanced Liver Cancer, Advanced Hepatic Carcinoma | NCT02624700(2015); NCT04163237(2019); NCT03164382(2017); NCT03211416(2017) |
| MEK inhibitor | Trametinib | Advanced ALK-Positive NSCLC, Advanced/Metastatic Colorectal Cancer | NCT03087448(2017); NCT03714958(2018) | |
| Inhibitors of transcription factors that indirectly induce EMP | ||||
| JAK and STAT3 inhibitors | Small molecule inhibitor | STAT3: BB1608 (Napabucasin) | Metastatic Colorectal Cancer, Metastatic Pancreatic Cancer | NCT03522649(2018); NCT03647839(2018); NCT03721744(2018) |
| Compounds acting on epigenetic modulators | ||||
| Histone deacetylase inhibitor | Vorinostat | Mutated Advanced Melanoma, Breast Cancer Metastatic | NCT02836548(2016); NCT03742245(2018) | |
| Romidepsin | Survey- Relapsed or Refractory Peripheral T-Cell Lymphoma | NCT03742921(2018); NCT03547700(2018) | ||
| Mocetinostat | Advanced Lung Cancer, Unresectable Stage III or Stage IV Melanoma | NCT03220477(2017); NCT03565406(2018) | ||
| Panobinostat | Multiple Myeloma | NCT02722941(2016); NCT04150289(2019); | ||
| Histone methyl transferases inhibitor | EZH2 inhibitor | E7438 (Tazemetostat, EPZ-6438) | Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma, Relapsed/Refractory Follicular Lymphoma | NCT03009344(2017); NCT03456726(2018); NCT04224493(2020) |
| EZH1/2 inhibitor | DS-3201b | Relapsed or Refractory Adult T-cell Leukemia/Lymphoma, Acute Leukemia Myeloid Leukemia, Acute Lymphocytic, Recurrent Small Cell Lung Cancer | NCT04102150(2019); NCT03110354(2017); NCT03879798(2019) | |
| Inhibitors of stimuli from the tumor microenvironment | ||||
| HIF-1α inhibitors | Small molecule inhibitor | PT2385 | Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma, Recurrent Glioblastoma | NCT03108066(2017); NCT03216499(2017) |
| Digoxin | Breast Cancer, Circulating Tumor Cells (CTCs), Advanced Pancreatic Cancer, Advanced Solid Tumor | NCT03928210(2019); NCT03889795(2019) | ||