Targeted Therapy for Hepatocellular Carcinoma: Old and New Opportunities

Abstract

Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver, accounting for 90% of all recorded cases. HCC is the third most common cause of cancer-related death, with a 5-year survival rate of just 3%. In the advanced stages, systemic treatments allow doctors to obtain clinical benefits, although the prognosis remains very poor. In the past few decades, new molecular targeted therapies against receptor tyrosine kinases have been developed and clinically evaluated. Sorafenib was the first oral tyrosine kinase inhibitor (TKI) approved for the treatment of advanced HCC in 2007. Subsequently, other TKIs, including Cabozantinib, Regorafenib, Lenvatinib, and vascular endothelial growth factor receptor (VEGFR) inhibitors such as Ramucirumab and VEGF inhibitors such as Bevacizumab have been approved as first- or second-line treatments. More recently, the combination of immune checkpoint inhibitors and VEGF inhibitors (Atezolizumab plus Bevacizumab) have been analyzed and approved for the treatment of advanced HCC. On the basis of the poor prognoses and the meager benefits deriving from the available systemic therapies, research into new treatments is extremely necessary. In this review, we focus on the available systemic therapies for advanced HCC, with a look toward the future.

SPATS2 is correlated with cell cycle progression and immune cells infiltration in hepatocellular carcinoma

“…It is well known that the immune system plays an important role in controlling cancer progression. Recent year, immunotherapy has developed as the new first-line treatment option for advanced HCC [ 4 , 21 , 22 ]. Previous study indicated that tumor immune cell infiltration generates an immunosuppressive TME and presences a generally correlations with a worse prognosis [ 23 , 24 ].…”

“…It is the sixth most commonly diagnosed malignancy and the third leading cause of cancer-related mortality worldwide [ 2 , 3 ]. In the past few decades, new therapeutic strategy, such as molecular targeted therapies and immunotherapy, have been developed and clinically evaluated with interesting results in HCC [ 4 ]. Remarkably, the combination of immune checkpoint inhibitors and VEGF inhibitors (Atezolizumab plus Bevacizumab) have been tested and approved for the treatment of advanced HCC [ 5 ].…”

Identification of a nucleotide metabolism-related signature to predict prognosis and guide patient care in hepatocellular carcinoma

“…Hepatocellular carcinoma (HCC) is the most common subtype of primary liver malignancy, often accompanied by cirrhosis and chronic hepatitis ( Forner et al, 2018 ; Llovet et al, 2022 ). Despite significant advances in the diagnosis and treatment of liver cancer, long-term survival remains poor ( Laface et al, 2022 ). Because of the hidden origin of liver cancer, many patients are diagnosed at a late stage ( Singal et al, 2020 ).…”

Efficacy and Prognostic Factors of Regorafenib in the Treatment of BCLC Stage C Hepatocellular Carcinoma After Failure of the First-Line Therapy

“…Tyrosine kinase inhibitors (TKIs), such as sorafenib, lenvatinib, and donafenib have improved the clinical efficacy of HCC and prolonged the survival time of patients with advanced HCC. [7][8][9][10] Meanwhile, TACE combined with these anti-angiogenic drugs can reduce the expression level of vascular endothelial growth factor (VEGF), reduce the incidence of tumor recurrence and metastasis, and improve the efficacy of TACE. 11 Regorafenib is an oral multi-kinase inhibitor that blocks a variety of protein kinases related to tumor angiogenesis, cell proliferation, tumor metastasis, and immunity.…”