hepatocellular carcinoma

Byaibio

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is a major disease context for immunotherapy, locoregional therapy, and precision oncology. It is driven by mechanisms including alpha fetoprotein-PI3K/Akt–linked cancer stemness, immune escape programs involving setdb2, spp1, and rnaseh2c, and regulated cell-death biomarkers such as cep55, dlgap5, and ezh2. Recent work also highlights intratumour ploidy heterogeneity and clonal evolution, as well as ductular reaction–associated immunosuppression and cholic acid-mediated immune effects. Therapeutically, HCC is treated with transarterial chemoembolization for intermediate-stage disease, with newer strategies aiming to improve TACE efficacy, and it remains a key setting for immune checkpoint inhibitors, anti pd 1, nivolumab, lenvatinib, and conversion therapy approaches. Emerging advances include nanodelivery platforms targeting gpc3, hypoxia-activated tirapazamine combinations, ferroptosis-based regimens with rsl3 and sulfasalazine, and microbiome or small-molecule strategies such as phenethyl isothiocyanate and saquinavir.

Immunotherapy and immune escape

  • A 2026 Cancer Letters study (PMID:41786278) showed that targeting FGFR1-regulated spp1 signaling repolarized immunosuppressive macrophages and sensitized HCC to anti pd 1 therapy.
  • A 2026 Journal for Immunotherapy of Cancer paper (PMID:41986071) reported that rnaseh2c drove proliferating macrophage-mediated immunosuppression and HCC progression through a Cdk9 axis and CCL2/CCR2-linked CD8+ Tex infiltration.
  • A 2026 Cancer Immunology, Immunotherapy study (PMID:41961075) proposed st3gal1 inhibition to downregulate Siglec-7 ligands and reverse immune escape in HCC.
  • A 2026 Cancer Research paper (PMID:41570324) found that intratumoral lactobacillus johnsonii enhanced sensitivity to PD-1 blockade by expanding CD8+ T cells in HCC.

Locoregional therapy and conversion strategies

Molecular profiling, biomarkers, and prognosis

  • A 2026 Journal of Hepatology study (PMID:41297676) examined intratumour ploidy heterogeneity and clonal evolution in HCC, with prognostic relevance.
  • A 2026 Cellular Signalling paper (PMID:41651174) identified alpha fetoprotein as a key regulator of cancer stemness via PI3K/Akt signaling.
  • A 2026 Naunyn-Schmiedeberg’s Archives of Pharmacology study (PMID:41984188) linked cep55, dlgap5, and ezh2 to regulated cell death and immunotherapy resistance.
  • A 2026 Oncogene paper (PMID:41946995) showed that setdb2 promoted immunosuppression through abnormal SHP-1 splicing in HCC.

Targeted, repurposed, and experimental therapies

  • A 2026 Free Radical Biology & Medicine study (PMID:41687749) showed that saquinavir induced pyroptosis via the OTUD5-JAK1-GSDME axis and was evaluated with sorafenib.
  • A 2026 Phytotherapy Research paper (PMID:41983254) found that phenethyl isothiocyanate suppressed HCC progression and immune evasion through ZNF652/PD-L1 regulation.
  • A 2026 ACS Applied Materials & Interfaces study (PMID:42027106) developed a gpc3-targeted nanoplatform for synergistic ferroptosis, photothermal therapy, and immunotherapy.
  • A 2026 Journal of Materials Chemistry B study (PMID:42017284) used a tirapazamine-assembled platform for combined chemotherapy, photodynamic therapy, and photothermal therapy in hypoxic HCC.