Table 1.
Potential impact of targeted therapies and their combinations on ECM components in HCC
| Targeted therapies | Pharmacological target | Affected ECM protein |
|---|---|---|
| Single-agent ICI | ||
| Pembrolizumab | PD-1 | TGF-β1143 |
| Nivolumab | PD-1 | collagen144,145 |
| Dostarlimaba | PD-1 | collagen144,145 |
| Durvalumaba | PD-L1 | collagen144,145 |
| Combination ICI therapies | ||
| Atezolizumab + bevacizumab | PD-L1 + VEGF | VEGF, fibronectin,146 collagen144,145 |
| Ipilimumab + nivolumab | CTLA-4 + PD-1 | pro-collagen type-III147 |
| Durvalumab + tremelimumab | PD-L1 + CTLA-4 | pro-collagen type-III147 |
| Pembrolizumab + lenvatinib | PD-1 + TKI | collagen144,145 |
| Atezolizumab + cabozantinib | PD-L1 + TKI | collagen144,145 |
| Other targeted therapies | ||
| Sorafenib | multiple receptor tyrosine kinases (RTKs) | agrin, VEGF5,77 |
| CAR T cell therapy | immunotherapy | GPC371,73 |
| GC33 | monoclonal antibodies | GPC371,73 |
| GPC3 peptide vaccine | vaccines | GPC371,73 |
| Recombinant endostatin | peptides | VEGF (ClinicalTrials.gov: NCT03208335) |
| ACEi and ARBs | RASis | collagen, hyaluronic acid140 |
a
In view of the lack of evidence for HCC-specific studies, the role of collagen as a key mediator of anti-PD-1 (dostarlimab) and anti-PD-L1 (durvalumab) resistance remains speculative.