Pregnane X receptor mediates sorafenib resistance in advanced hepatocellular carcinoma.

// Xiao-Xiao Ding 1, * , Qing-Ge Zhu 1, * , Shi-Ming Zhang 1, * , Lei Guan 1 , Ting Li 1 , Lei Zhang 1 , Shi-Yang Wang 2 , Wan-Li Ren 2 , Xue-Mei Chen 1 , Jing Zhao 1 , Song Lin 1 , Zhi-Zhen Liu 1 , Yan-Xia Bai 2 , Bing He 1 and Hu-Qin Zhang 1 1 The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, P. R. China 2 Department of Otorhinolaryngology - Head and Neck Surgery, The First Affiliated Hospital, Jiaotong University, Shaanxi 710061, P. R. China * These authors have contributed equally to this work Correspondence to: Hu-Qin Zhang, email: huqzhang@mail.xjtu.edu.cn Bing He, email: hebinghb@mail.xjtu.edu.cn Yan-Xia Bai, email: yanxiab@126.com Keywords: hepatocellular carcinoma, driver mutations, driver identification, targeted therapy, precision medicine Received: March 31, 2017     Accepted: May 10, 2017     Published: June 06, 2017 ABSTRACT Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called “driver mutations”. The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy. In this review, we summarized currently discovered driver mutations and corresponding signaling pathways, made an overview of identification methods of driver mutations and genes, and classified targeted drugs for HCC. The knowledge of mutational landscape deepen our understanding of carcinogenesis and promise future precision medicine for HCC patients.

Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy

// Yinlong Kong 1 , Lin Sun 1 , Zhenyu Hou 1 , Yongqiang Zhang 1 , Ping Chen 1 , Yunlong Cui 1 , Xiaolin Zhu 1 , Tianqiang Song 1 , Qiang Li 1 , Huikai Li 1 , Ti Zhang 1 and Lunxiu Qin 2, 3 1 Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin 300060, China 2 Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai 200040, China 3 Cancer Research Center, Institute of Biomedical Science, Fudan University, Shanghai 200032, China Correspondence to: Ti Zhang, email: zhangti@tjmuch.com Huikai Li, email: tjchlhk@126.com Lunxiu Qin, email: qinlx99@vip.163.com Keywords: apatinib; hepatocellular carcinoma; vascular endothelial growth factor receptor Received: May 24, 2017     Accepted: September 21, 2017     Published: November 06, 2017 ABSTRACT As treatment options for hepatocellular carcinoma (HCC) are currently limited, we evaluated the efficacy and safety of oral apatinib, a VEGFR-2 inhibitor, on patients with advanced HCC. Twenty-two patients from Tianjin Medical University Cancer Institute and Hospital were enrolled for evaluation. Apatinib was administered at 500 mg/day or 250 mg/day continuously. Clinical endpoints were time to disease progression (TTP), overall survival (OS), and safety. The median TTP of treated patients was 10.4 months (95% CI 3.4 -17.5). At the last follow-up, 50% patients had survived longer than 11.4 months from the first dose. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) rates were 0%, 40.9%, 40.9%, and 18.2%, respectively. The most common apatinib-related adverse events were hand-foot skin reaction (HFSR) (81.8%) and diarrhea (77.3%). Hypertension (27.3%) and HFSR (13.6%) were the most frequent grade 3/4 adverse events. In summary, results of this small study indicate that apatinib is well tolerated and extremely effective for the treatment of advanced HCC. It is therefore imperative to design and carry out well-controlled clinical trials to confirm its efficacy.

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Apatinib is effective for treatment of advanced hepatocellular carcinoma.

miR-122 enhances sensitivity of hepatocellular carcinoma to oxaliplatin via inhibiting MDR1 by targeting Wnt/β-catenin pathway

Apatinib (Aitan®, brand name in China) is a new anti-antiangiogenic agent that has recently been approved for the treatment of advanced gastric cancer (GC) in China. Nevertheless, its therapeutic efficacy against other types of advanced solid tumors remains unclear. This meta-analysis examines the short-term efficacy and safety of apatinib or combination therapy for GC, hepatocellular carcinoma (HCC) and non-small-cell lung cancer (NSCLC); and provides a discussion of its anti-angiogenesis therapy applications. Seven clinical studies met the inclusion criteria. The treatment of cancers using apatinib was more successful compared to therapy without apatinib. Both objective response rates (ORRs) and disease control rates (DCRs) were significantly improved in the apatinib group compared to those in the control group (RR=2.18, 95% CI 1.30-3.65; RR=2.09, 95% CI 1.21-3.60). The DCR of 850 mg qd and 750 mg qd were higher than those in the control group (P<0.05). Based on the short-term acute adverse reactions of apatinib, significant differences between groups were found for hypertension, urine protein, hand foot syndrome, and gastrointestinal reactions (diarrhea), while no significant differences were found for myelosuppression, nausea and vomiting. Moreover, the results showed that apatinib prolonged patient survival (HR=0.38, 95% CI: 0.28-0.52), and the effect was more pronounced in patients treated with 750 mg qd or 850 mg qd of apatinib than in those treated with a dose of ≤500 mg qd. Additionally, compared to its second-line application, the third-line application was shown to further reduce the risk ratio in patients. Furthermore, overall survival was longer in patients treated with apatinib. Apatinib was shown to have certain short-term effects and survival benefits on GC, HCC, and NSCLC with controllable adverse effects.

/pdf/efficacy-and-safety-of-apatinib-treatment-for-gastric-cancer-4t5rrasjzr.pdf

Efficacy and safety of apatinib treatment for gastric cancer, hepatocellular carcinoma and non-small cell lung cancer: a meta-analysis.

// Peisi Kou 1,2,* , Yan Zhang 2,* , Wenbo Shao 4 , Hui Zhu 2 , Jingze Zhang 2 , Haiyong Wang 2 , Li Kong 2 and Jinming Yu 2,3,1 1 Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2 Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China 3 School of Medicine and Life Sciences, University of Jinan - Shandong Academy of Medical Sciences, Jinan, China 4 Department of Intervention, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China * These authors have contributed equally to this work Correspondence to: Jinming Yu, email: // Keywords : hepatocellular carcinoma, apatinib, targeted therapy Received : September 06, 2016 Accepted : January 04, 2017 Published : January 18, 2017 Abstract Apatinib is a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. Previous studies have suggested that apatinib is safe and effective in some solid tumors. We report one case with advanced hepatocellular carcinoma (HCC), who received apatinib combined with transhepatic arterial chemotherapy and embolization (TACE), and chemotherapy respectively. TACE was administered three times once a month, using lipiodol 10ml, oxaliplatin 150mg, and tegafur 1g. The dose of apatinib was 500 mg/d from day 4 to 24. After TACE, the patient received chemotherapy of regimen FOLFOX4, oxaliplatin intravenously at 85 mg/m 2 on day 1, calcium levofolinate 200 mg/m 2 on day 1 and 2, 5-fluorouracil 400 mg/m 2 intravenously and 5-fluorouracil 600 mg/m 2 intravenously pumped for 22h on day 1 and 2, cycled every two weeks for seven cycles. He took concurrently apatinib with a dose of 500mg daily from 1 to 10 days per cycle. He was confirmed as partial response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST). The level of serum alpha-fetoprotein (AFP) decreased from 60500 ng/ml to 12.7 ng/ml, and the progression free survival (PFS) time was more than eight months. It indicated that apatinib may be a superior choice for HCC patients.

/pdf/significant-efficacy-and-well-safety-of-apatinib-in-an-329h311c3q.pdf

Wenbo Shao

Papers

Significant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review.