Table 2 Clinical trials of cancer therapies targeting ECM and ECM-associated molecules.
From: Concepts of extracellular matrix remodelling in tumour progression and metastasis
Target | Agent | Effect on ECM | Cancer type | Status | Ref. |
|---|---|---|---|---|---|
MMP-2 and MMP-9 | COL-3 (Incyclinide) | Inhibit MMP activity and expression leading to reduced ECM remodelling and angiogenesis | Refractory metastatic cancer | Completed phase I | NCT00001683a |
MMP-9 | Andecaliximab (anti-MMP-9 mAb) in combination therapy | Inhibit MMP-9 remodelling of ECM | Advanced gastric or gastroesophageal junction adenocarcinoma | Failed phase III | NCT02545504 |
(GS) 5745 (anti-MMP-9 mAb) in combination with bevacizumab (anti-VEGF) | Inhibit angiogenesis via inhibition of MMP-9 remodelling of ECM | Recurrent glioblastoma | Ongoing phase I | NCT03631836 | |
MT1-MMP | BT1718 (drug conjugate) | Induce cell death in MT1-MMP expressing cells | Advanced solid tumours | Ongoing phase I/II | NCT03486730 |
ADAM10 and ADAM17 | INCB007839 (aderbasib) in combination with rituximab (anti-CD20) | Decrease cell surface protein degradation and prevent oncogenic signalling from EGFR and Notch pathways | Diffuse large B-cell Non-Hodgkin lymphoma | Completed phase II | NCT02141451 |
INCB007839 (aderbasib) | Prevents NLGN3 release into the tumour microenvironment to limit tumour growth | Children with recurrent/progressive high-grade gliomas | Ongoing phase I | NCT04295759 | |
LOX and LOXLs | Tetrathiomolybdate (nonspecific copper chelator) | Chelate copper, which lowers serum LOXL2 concentrations275 | Moderate to high risk primary breast cancer | Ongoing phase II | NCT00195091 |
Tetrathiomolybdate in combination with Carboplatin/Pemetrexed | Chelate copper, which lowers serum LOXL2 concentrations | Metastatic non-small-cell lung cancer | Completed phase I | NCT01837329 | |
AB0024 (anti-LOXL2 mAb) | Inhibit LOXL2 activity resulting in decreased collagen cross-linking and decreased fibroblast activation | Advanced solid tumours | Completed phase I | NCT01323933 | |
Heparanase | SST0001 (Ronespartat, a chemically modified heparin) | Inhibit heparanase activity resulting in decreased angiogenesis | Advanced, heavily pretreated refractory multiple myeloma | Completed phase I | NCT01764880 |
HA | PEGPH20 (recombinant human hyaluronidase) in combination therapy | Degrade hyaluronan | Stage IV untreated pancreatic ductal adenocarcinoma (PDA) | Terminated phase III | NCT02715804a |
TGF-β | Losartan (angiotensin II receptor agonist) in combination therapy | Decrease TGF-β expression, which leads to reduced pro-tumourigenic ECM remodelling including secretion of collagen I | Locally advanced pancreatic cancer | Ongoing phase II | NCT01821729 |
Fresolimumab (GC1008, anti-TGF-β mAb) in combination therapy | Prevent fibrosis associated with radiation therapy in breast cancer | Metastatic breast cancer | Completed phase II | NCT01401062 | |
Fresolimumab (anti-TGF-β mAb) in combination therapy | Prevent fibrosis associated with radiation therapy in early stage non-small-cell lung carcinoma | Stage IA-IB non-small-cell lung cancer | Ongoing phase I/II | NCT02581787 |
