Advanced Hepatocellular Cancer: the Current State of Future Research

Abstract

Hepatocellular carcinoma is a common malignancy worldwide, rapidly rising in incidence. While there have been some developments in advancing therapeutic options in this disease, these have admittedly been modest to date, and as a result, this is a patient population with an inherently poor prognosis. Currently, sorafenib remains the only established systemic therapy proven to increase the overall survival of patients with advanced disease. The approval of sorafenib in 2007 ushered in the era of targeted therapies. Several phase 2 and 3 clinical trials have failed however to improve on sorafenib in the first-line setting, and no single agent has been demonstrated to impact outcomes after sorafenib failure. Having reached somewhat of an impasse in terms of drug development in hepatocellular carcinoma, enthusiasm in the field has moved toward innovative approaches such as molecular characterization and immunotherapy in an attempt to impact survival. This review highlights the current endeavors in terms of experimental research for patients with advanced hepatocellular carcinoma.

Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging

“…Tumours with high intra-tumour heterogeneity generally have a poorer prognosis, which may be secondary to a more aggressive biology or treatment resistance 56 . The observed correlations between MRI features and the expression of potential therapeutic markers for targeted molecular or immunotherapy of HCC 57 suggest that the proposed mpMRI histogram analysis could be used to noninvasively predict treatment outcome at baseline. Knowledge of the expression of therapeutic targets using non-invasive imaging could aid in the stratification of patient-tailored, personalized treatment.…”

Morusin shows potent antitumor activity for human hepatocellular carcinoma in vitro and in vivo through apoptosis induction and angiogenesis inhibition

“…Less than 20% of HCC patients are amenable to surgical resection or liver transplantation owing to the discovery or diagnosis of HCC at advanced stages. Even worse, therapeutic strategies including chemotherapy and radiation have limited impact on the survival of HCC patients because of their limitations with regard to efficacy and side effects 1,3,4. Therefore, the current study focused on identifying more effective therapeutic options for HCC.…”

“…This results partly from the diagnosis in advanced stages and the consequent loss of therapeutic opportunity 3. Moreover, because of their low response rate and high toxicity, many chemotherapy agents are of limited use and provide minimal benefit to survival time in HCC patients 4,5. Therefore, there is an urgent need to explore more effective therapeutic strategies for HCC patients.…”

Recent advances in hepatocellular carcinoma therapy

“…Other small molecule targeted therapies such as doxorubicin, gefitinib, vatalanib, cediranib, bortezomib (proteasome inhibitor), rapamycin, sirolimus, and gemcitabine as single agent or in combination with mAb have been evaluated in clinical trials targeting pathways which are activated in HCC (Spangenberg et al, 2009). Connell and colleagues have extensively reviewed the current clinical trials of HCC therapeutics which are underway along with their placebo studies in parallel (Connell, Harding, & Abou-Alfa, 2016). Other BCR/ABLand c-Kit inhibitors recently under phase II clinical trials (dasatanib, imatinib) yielded mixed results when compared as single or combination drugs.…”