Tamibarotene: a new hope for therapeutic efficacy in hepatocellular carcinoma patients.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common health threats worldwide. HCC is characterized by silent development and poor prognosis as well as 5-year survival rates of \5 %. The incidence and mortality rates of HCC are increasing in many countries, especially in Asian populations. The major risk factors for HCC development are hepatitis B and C viral infections, which contribute to 75 % of HCC cases. Other etiological factors, such as alcohol consumption, aflatoxin, obesity and diabetes, are also frequently observed in clinics [1, 2]. According to practice guidelines, treatment options include surgical resection, liver transplantation, percutaneous ablation, transarterial chemoembolization (TACE) and percutaneous ethanol injection, which are selected by hepatologists based on staging of primary HCC. In the early stage, surgical resection remains the most effective treatment with 40–70 % 5-year survival rates; however, only 10–20 % of the subjects with HCC are eligible for surgical resection because of poorly preserved liver function, portal vein invasion or extrahepatic spread [3]. TACE is recommended as the first-line treatment for HCC patients with intermediate stage disease and for downstaging tumors that exceed the criteria for transplantation [1]. One randomized trial evaluated the survival benefit with TACE and found that TACE-treated patients had a prolonged 2-year survival of 63 % compared with 27 % with only a supportive care [4]. Transarterial radioembolization (TARE) is based on the injection of radiolabeled particles through the hepatic artery into the in situ tumor and has become another option for patients with intermediate-stage HCC in recent years [5]. A long-term follow-up check study demonstrated that TARE was well tolerated, with significantly lower rates of abdominal pain and elevated liver enzymes, but median survival was not significantly increased compared with TACE-treated patients [6]. Although improvements have been made in the treatment of HCC, the incidence and mortality rates of HCC are still increasing. This may be partially accounted for by the fact that most HCC patients are diagnosed at advanced stages [5]. Unfortunately, the available therapies for patients with advanced HCC are extremely limited. Sorafenib is a new multi-target drug that blocks tumor angiogenesis and proliferation by inhibiting the components of the Raf signaling pathway [7]. The safety and efficacy of sorafenib in the treatment of advanced HCC has been demonstrated in some recent clinical trials [8–11]. It improved the median survival time by *3 months (the median for sorafenib was 10.7 months, while the median for the placebo group was 7.9 months) in patients with advanced HCC [10]. However, there is still a lack of significant treatment efficacy according to the response evaluation criteria in solid tumors (RECIST) [3]. In addition, the application of sorafenib was limited because of severe adverse events, including skin rash, hand-foot skin reactions, diarrhea and hypertension. Other potential treatments for advanced HCC, such as gene therapy and immunotherapy, are still under investigation and may be accepted as adjuvant therapies. Therefore, it is of great interest to develop more effective and practical therapeutic strategies for advanced HCC patients. Tamibarotene (4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl2-naphthyl] carbamoyl benzoic acid) is a synthetic retinoid that selectively binds to retinoic acid receptors [12]. Compared to all-trans retinoic acid, tamibarotene is chemically J. Fu J.-Y. Zhang F.-S. Wang (&) Research Center for Biological Therapy, Beijing 302 Hospital, Institute of Translational Hepatology, Beijing 100039, People’s Republic of China e-mail: fswang302@163.com

DOI: 10.1007/s12072-013-9493-5

Cite this paper

@article{Fu2014TamibaroteneAN, title={Tamibarotene: a new hope for therapeutic efficacy in hepatocellular carcinoma patients.}, author={Junliang Fu and Ji-yuan Zhang and Fu-Sheng Wang}, journal={Hepatology international}, year={2014}, volume={8 1}, pages={1-3} }