Liver cancer: Targeted future options

Abstract

Hepatocellular carcinoma (HCC) has a poor prognosis and systemic chemotherapies have disappointing resul ts. The increasing knowledge of the molecular biology of HCC has resulted in novel targets, with the vascular endothelial growth factor and epidermal growth fac tor receptor (EGFR)related pathways being of special interest. New blood vessel formation (angiogenesis) is essential for the growth of solid tumors. Antiangiogenic strategies have become an important therapeutic mo dality for solid tumors. Several agents targeting angio genesisrelated pathways have entered clinical trials or have been already approved for the treatment of solid tumors. These include monoclonal antibodies, receptor tyrosine kinase inhibitors and immunomodulatory drugs. HCC is a highly vascular tumor, and angiogenesis is be lieved to play an important role in its development and progression. This review summarizes recent advances in the basic understanding of the role of angiogenesis in HCC as well as clinical trials with novel therapeutic approaches targeting angiogenesis and EGFRrelated pathways.

Mucin Glycosylating Enzyme GALNT2 Regulates the Malignant Character of Hepatocellular Carcinoma by Modifying the EGF Receptor

“…Because many substrates for GALNT2 are present in HCC cells, it remains possible that GALNT2 mediates its effects through other receptors in addition to EGFR. EGFR inhibitors prevent the development of HCC in animal models (26) and erlotinib has shown some activity in the treatment of human HCC (16,27). Sorafenib, a multikinase inhibitor, has been shown to provide a significant survival benefit for patients with advanced HCC (28).…”

Targeting the vasculature of visceral tumors: novel insights and treatment perspectives

“…The agent has been approved by the FDA for the treatment of renal cell carcinoma and refractory gastrointestinal stroma tumors [27]. Adverse effects were fatigue, hypertension, and skin toxicity, which are typical for VEGFR tyrosine kinase inhibitors.…”

“…Besides antibody-based antiangiogenic agents, smallmolecule VEGF receptor tyrosine kinase inhibitors are another leading class of antiangiogenic drugs that have been investigated intensively in several preclinical and clinical studies in the last years: Sorafenib (Nexavar®) inhibits VEGF receptor 1-3, platelet-derived growth factor (PDGF) receptor β, Flt-3, and c-kit [26] and has verified activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) [27]. Sorafenib was well tolerated with a maximal tolerated dose of 400 mg twice daily.…”

“…Sunitinib, as another TKI, showed an overall survival benefit for advanced HCC as well [27]. For this reason, a direct comparison of sunitinib and sorafenib in a randomized phase III trial for advanced HCC was performed.…”

The 786-0 renal cancer cell-derived exosomes promote angiogenesis by downregulating the expression of hepatocyte cell adhesion molecule

“…Vessels are markedly associated with the pathogenesis and development of tumors and it has been demonstrated that cells at the preneoplastic stage must acquire angiogenic capacity to become malignant cells. Without blood vessels, tumors cannot grow and form metastases (12)(13)(14). Vascular endothelial growth factor (VEGF) is the most important factor for the induction and regulation of proliferation of vascular endothelial cells as well as angiogenesis in physiological and pathological conditions.…”