Abstract
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer related mortality worldwide. The incidence of HCC has been increasing annually. Viral infection, alcohol usage, and other causes of cirrhosis have been identified as major risk factors for HCC development. The underlying pathogenesis has not been as well defined. There have been multiple hypotheses to the specific mechanisms of hepatocarcinogenesis and they share the common theme of chronic inflammation, increase oxidative stress, and genomic alteration. Therapeutic options of HCC have been primarily local and/or regional including transplantation, resection, and radial frequency ablation, chemoembolization or radio-embolization. For unresectable or metastatic disease, the options are limited. Conventional chemotherapeutic options have been noted to have limited benefit. Sorafenib has been the one and only systemic therapy which has demonstrated modest overall survival benefit. This has led to more extensive research with focus on targeted therapy. Numerous pre-clinical and early phase clinical studies have been noted but failed to show efficacy in later phase clinical trials. In an effort to identify new potential therapeutic options, new understanding of underlying pathways to hepatocarcinogenesis should be one of the main focuses. This leads to development of more molecularly targeted agents to specific pathways, and immunotherapy. This article provides a review of major studies of molecular targeted agents which attempts to target these specific pathways in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the seventh most common cancer in the world and the third in cancer related mortality in adults worldwide [1]
These mechanisms suggest some common theme to hepatocarcinogenesis pathway including p53 inactivation or mutation, chronic inflammation leading to persistent hepatocyte necrosis and regeneration causing genetic alteration, and oxidative stress leading to mutagen and fibrosis which can lead to more genetic alteration [16]
The combination of 5-fluorouracil with oxaliplatin was studied in Asia with 371 patients of advanced HCC and showed a median overall response rate (ORR) of 8%, median progression free survival (PFS) was 2.93, and median overall survival (OS) was
Summary
Hepatocellular carcinoma (HCC) is the seventh most common cancer in the world and the third in cancer related mortality in adults worldwide [1]. Selected patients with localized disease may be treated with curative intents with resection, liver transplantation, or local therapy [4]. The five year survival of patient who undergo surgical resection is about 42%–67% [5]. Liver transplantation may be a potential therapeutic option for those patients who are not candidates for resection but still have localized disease. Liver transplantation in HCC have been shown to have a five year survival up to 75% [6,7,8]. For patients who do not meet criteria for resection or transplantation, nonsurgical local-regional therapies such as transarterial chemoembolization (TACE), radioembolization, cryoablation, and radioablation could be effective. System therapy with chemotherapy has not shown significant effect on survival. Immunotherapy with checkpoint inhibition has revealed very encouraging data in HCC therapy recently
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