Therapeutic Strategies for Hepatocellular Carcinoma: New Advances and Challenges

Abstract

Hepatocellular carcinoma (HCC) is the fastest growing malignancy in the USA, and its prognosis remains poor with a 5-year survival around 12 %. Clinical data demonstrate that 85 % of cases occur in individuals with underlying cirrhosis and only 15 % develop in non-cirrhotic livers. Therefore, American and European guidelines recommend routine HCC screening for high-risk individuals (patients with cirrhosis) with abdominal ultrasound every 6 months. Once a lesion is identified or suspected on ultrasound, dynamic imaging is then indicated. The diagnosis of HCC is established in a patient with cirrhosis when a lesion measures at least 1 cm in diameter and demonstrates arterial enhancement and portal venous washout on contrast-enhanced computerized tomography or magnetic resonance imaging. Indeterminate lesions should be followed with surveillance imaging or further investigated with biopsy according to the level of suspicion for malignancy. Given the clinical, pathological, and molecular heterogeneity of HCC, there are multiple therapeutic modalities available. These may be curative, such as surgical resection, liver transplantation, and local ablation, or palliative, such as catheter-directed therapies (transarterial chemo, radio, or bland embolization), and systemic therapy (sorafenib). Patients with a single lesion, good performance status, and preserved liver synthetic function should be offered curative surgical resection or ablation therapy. Patients with HCC and decompensated liver disease should be evaluated and listed for liver transplantation. For unresectable disease or tumor burden precluding transplantation or curative ablation, palliative therapeutic modalities should be offered. Sorafenib is indicated for patients with vascular invasion and/or extra-hepatic metastasis if the estimated life expectancy is more than 3 months. Systemic internal radiation therapy using yttrium-90 microspheres in cases of multifocal bi-lobar disease and/or portal vein occlusion is an emerging therapy. Best supportive care is recommended for patients who lack the hepatic reserve to tolerate therapy.

Expression profile and prognostic value of glypican‐3 in post‐operative South Korean hepatocellular carcinoma patients

“…Our own case series included patients who underwent various anti-cancer treatments such as TACE and RFA, while some prognostic studies enrolled patients with no prior treatment (15,18). However, we did not find 1 Determined by log-rank test for comparison of overall survival and disease-free survival between GPC3-positive and GPC3-negative group. differences in GPC3 positivity based on prior treatment in our subjects (data not shown).…”

Treating hepatocellular carcinoma with 90Y-bearing microspheres: a review

“…Although SIRT with 90 Y-bearing microspheres has an acceptable safety profile, studies comparing 90 Y-bearing microspheres to other palliative loco-regional therapies and thus consensus about the optimal use of 90 Y-bearing microspheres are currently lacking [31]. However, SIRT with 90 Y-bearing microspheres, especially with the glass-based microspheres, because of their low embolic potential, may be preferred to transarterial chemoembolization (TACE) in the presence of portal vein occlusion [32-34].…”

Upregulation of UBE2Q1 via gene copy number gain in hepatocellular carcinoma promotes cancer progression through β‐catenin‐EGFR‐PI3K‐Akt‐mTOR signaling pathway

“…Only a small percentage of HCC is diagnosed at an early stage and amenable to potential curative treatments, such as surgical resection, liver transplantation, and radiofrequency ablation . The prognosis is quite dismal for advanced stage HCC patients who have unresectable tumors because it is a clinically, pathologically, and molecularly heterogeneous disease and is one of the few solid organ malignancies resistant to conventional chemotherapy . Sorafenib, a multi‐tyrosine kinase inhibitor, is the only chemotherapeutic drug available for the treatment of unresectable HCC .…”

“…4 Sorafenib, a multi-tyrosine kinase inhibitor, is the only chemotherapeutic drug available for the treatment of unresectable HCC. 4 However, it has limited efficacy in improving survival of HCC patients, 5 most likely due to the activation of alternative pathways promoting the survival of tumor cells. 6 Thus, the development of novel treatment modalities against advanced HCC is mandatory.…”