Challenges of advanced hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials.

Targeting the correct target in HCC

“…The rates of incidence and mortality of HCC are increasing worldwide. Unfortunately, both figures are very similar mainly due to the longer survival of patients with cirrhosis, the aggressiveness of HCC and the lack of efficient therapies 1 2. Since 2008, sorafenib, a multikinase (BRAF/vascular endothelial growth factor receptor/platelet-derived growth factor receptor) inhibitor is the only approved systemic therapy for advanced HCC.…”

“…Sorafenib offers modest survival benefit, and recently some concerns about its cost-effectiveness have been raised 3. In the last years, many other molecular targeted agents have been tested for the treatment of HCC in different clinical trials with negative results 2 4…”

Long Non-Coding RNA Linc-USP16 Functions As a Tumour Suppressor in Hepatocellular Carcinoma by Regulating PTEN Expression

“…In recent years, specific surgery, radio frequency ablation, and chemotherapy have been common treatments for HCC [2, 3]. However, owing to disease recurrence and metastasis, the overall survival for HCC patients is still unsatisfactory.…”

Neoplastic macrovascular invasion represents an independent risk factor for dismal survival in sorafenib treatment for hepatocellular carcinoma

“…In developed countries there is the growing problem of cirrhosis developing in the setting of nonalcoholic fatty liver disease in patients with obesity, type 2 diabetes, dyslipidemia and hypertension [5][6][7][8] . Programs of sur veillance with upper abdomen ultrasound examination and characterization of focal liver lesions with computed tomography (CT) scan or magnetic resonance imaging (MRI) increase the rate of early diagnosis and curative treatments such as surgical resection, liver transplantation and locoregional ablative treatments [9][10][11][12][13] with improved survival. In the advanced stage, Barcelona Clinic Liver Cancer (BCLC) stage C, systemic therapy with sorafenib [14] represents the first line treatment for these patients, while regorafenib is available for second line as well as anti-PD-1 that has been recently approved by the Food and Drug Administration for HCC.…”