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Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

ABSTRACT: Cancer treatment has been revolutionized by the advent of new molecular targeted and immunotherapeutic agents. Identification of the role of tumor angiogenesis changed the understanding of many tumors. After the unsuccessful results with chemotherapy, sorafenib, by interfering with angiogenic pathways, has become pivotal in the treatment of hepatocellular carcinoma. Sorafenib is the only systemic treatment to show a modest but statistically significant survival benefit. All novel drugs and strategies for treatment of advanced hepatocellular carcinoma must be compared with the results obtained with sorafenib, but no new drug or drug combination has yet achieved better results. In our opinion, the efforts to impact the natural history of the disease will be directed not only to drug development but also to understanding the underlying liver disease (usually hepatitis B virus- or hepatitis C virus-related) and to interrupting the progression of cirrhosis. It will be important to define the role and amount of mutations in the complex pathogenesis of hepatocellular carcinoma and to better integrate locoregional and systemic therapies. It will be important also to optimize the therapeutic strategies with existing chemotherapeutic drugs and new targeted agents.

SUBMITTER: Montella L

PROVIDER: S-EPMC4945973 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

Montella Liliana L Palmieri Giovannella G Addeo Raffaele R Del Prete Salvatore S

World journal of gastroenterology 20160701 27

Cancer treatment has been revolutionized by the advent of new molecular targeted and immunotherapeutic agents. Identification of the role of tumor angiogenesis changed the understanding of many tumors. After the unsuccessful results with chemotherapy, sorafenib, by interfering with angiogenic pathways, has become pivotal in the treatment of hepatocellular carcinoma. Sorafenib is the only systemic treatment to show a modest but statistically significant survival benefit. All novel drugs and strat ...[more]

PMID: 27468204

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Project description:INTRODUCTION:serum alpha-fetoprotein (AFP) was routinely employed as a tumor marker for screening, diagnosis, and treatment follow-up of hepatocellular carcinoma (HCC). However, a substantial proportion of HCC patients had normal AFP level even at an advanced disease status. Few studies to date had tried to explore the nature and behavior of this normal AFP HCC (N-HCC). The purpose of this study was to investigate the clinicopathological characteristics and survival outcome of N-HCC after operation. In addition, potential tumor markers for N-HCC were also sought in an attempt to augment diagnostic ability. METHODS:between 2005 and 2015, patients with hepatocellular carcinoma who were treated with hepatectomy in Chang Gung Memorial Hospital Linkou branch were divided into two groups according to their preoperative serum AFP level (<15 ng/mL: NHCC; ?15 ng/mL: abnormal AFP HCC (A-HCC)). Patient demographic data and clinicopathological variables were collected. Kaplan-Meier and Cox regression multivariate analyses were performed to identify significant risk factors for disease-free survival (DFS) and overall survival (OS) for N-HCC. ELISA and immunohistochemical (IHC) studies were employed to determine the diagnostic accuracy of various tumor markers. RESULTS:a total of 1616 patients (78% male) who underwent liver resection for HCC were included in this study. Of them, 761 patients (47.1%) were N-HCC. N-HCC patients were significantly older with more comorbidities and less hepatitis virus infections. Furthermore, N-HCC had fewer early recurrences (49.6% vs. 60.8%, p < 0.001) and better DFS (44.6 months vs. 23.6 months, p < 0.001) and OS (94.5 months vs. 81.7 months, p < 0.001). Both ELISA and IHC studies demonstrated that glypican-3 (GPC3) would be a promising diagnostic tumor marker for N-HCC. CONCLUSION:N-HCC patients were significantly older and had less hepatitis virus infections or cirrhosis. Their tumors tended to be smaller, less vascular invaded, and well-differentiated. The carcinogenesis of N-HCC may thus not be identical to that of typical HCC. GPC3 would be a promising tumor marker for diagnosing N-HCC. Further study is warranted to validate our findings.

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Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

Publications

Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

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