TABLE 1.
Candidate therapies in CA based on mechanism and status of development
| Mechanism of Action | Therapy | Testing Status/Evidence | Reference |
|---|---|---|---|
| RhoA/ROCK inhibition | Atorvastatin | Preclinical (clinical trial phase I/IIa) |
Shenkar et al., 2019 Polster et al., 201875 |
| Fasudil | Preclinical | McDonald et al., 2012 | |
| BA-1049 (ROCK2 specific inhibitor) | Preclinical | McKerracher, et al. 2019* | |
| Inflammation | Anti-BR3 antibody (B-cell depletion) | Preclinical | Shi et al., 2016 |
| Reactive oxygen species | Vitamin D3 | Preclinical (clinical correlation in human) | Girard et al., 201633 Gibson et al., 2015 |
| Tempol | Preclinical (clinical phase I trial) | Gibson et al., 2015 | |
| Angiogenesis and VEGF inhibition | Propranolol | Case reports (open clinical trial) | Zabramski et al., 2016 |
| Bevacizumab, semaxanib (VEGF inhibition) | Preclinical | DiStefano et al., 2014 | |
| Delta-Notch | Sorafenib (multikinase inhibitor) | Preclinical | Wüstehube et al., 2010 |
| Endothelial-to-mesenchymal transition (TGF-β signaling cascade) | SB431542, LY364947 (SMAD) | Preclinical | Maddaluno et al., 2013 |
| Sulindac (p-catenin) | Preclinical | Bravi et al., 2015 | |
| DMH1 (BMP6) | Preclinical | Maddaluno et al., 2013 | |
| Restoration of autophagy (mTOR-ULK1) | mTOR inhibitors | Preclinical | Marchi et al., 2015 |
| MEKK2/ERK/KLF2–4 | TLR4 inhibition compounds | Preclinical | Tang et al., 2017 |
| BIX02189 (anti-MEK5) | Preclinical | Zhou et al., 2016 | |
| XMD17–109 (anti-ERK5) | Preclinical | Zhou et al., 2016 | |
| TSP-1 | TSP-1 replacement (TSR3) | Preclinical (clinical correlation in human) | Lopez-Ramirez et al., 2017 |
| TM and EPCR | TM and EPCR inhibitors | Preclinical (clinical correlation in human) | Lopez-Ramirez et al., 2019 |
| Microbiome | — | Preclinical | Tang et al., 2017 |
BMP6 = bone morphogenetic protein 6; BR3 = BLyS receptor 3/BAFF-R; Delta-Notch = Delta ligand–mediated Notch signaling; DMH1 = dorsomorphin homolog 1; EPCR = endothelial protein C receptor; ERK = extracellular signal–regulated kinase; KLF = Krüppel-like factor; MEK5 = dual specificity mitogen-activated protein kinase 5; mTOR = mammalian target of rapamycin; RhoA = Ras homolog gene family member A; ROCK = Rho-associated protein kinase; SMAD = transforming growth factor–beta signaling protein 1; TGF-β = transforming growth factor–beta; TM = thrombomodulin; TSP-1 = thrombospondin-1; TSR3 = transferase ribosome maturation factor 3; ULK1 = Unc-51 like autophagy activating kinase 1; — = not applicable.
Collaboration among BioAxone BioSciences, Inc., University of Chicago, Duke University, and LA BioMed.