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Shun Yamamoto, Shunsuke Kondo
Many clinical trials have been conducted with chemotherapies in patients with advanced hepatocellular carcinoma (HCC). However, few agents have shown efficacy. It is thought that the efficacy of some agents might have resulted from the heterogeneity of tumors, insufficient dosages due to liver cirrhosis, and post-therapy effects. In recent years, immune checkpoint inhibitors have shown promising clinical activity and safety in patients with advanced HCC. Areas covered: The authors provide an overview of chemotherapies used for the treatment of HCC, including ongoing trials...
June 18, 2018: Expert Opinion on Pharmacotherapy
Hitomi Takada, Masayuki Kurosaki, Hiroyuki Nakanishi, Yuka Takahashi, Jun Itakura, Kaoru Tsuchiya, Yutaka Yasui, Nobuharu Tamaki, Kenta Takaura, Yasuyuki Komiyama, Mayu Higuchi, Youhei Kubota, Wann Wang, Mao Okada, Nobuyuki Enomoto, Namiki Izumi
BACKGROUND: The present study aimed to investigate the impact of pre-sarcopenia on the prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. METHODS: We enrolled 214 patients (71 ± 10 years old; 166 men and 48 women; 90% Child-Pugh grade A and 10% Child-Pugh grade B) treated with sorafenib in our hospital from July 2009 to August 2016. The muscle volume was measured from CT images just before sorafenib administration using software (SliceOmatic)...
2018: PloS One
Hui Xie, Shengtao Tian, Haipeng Yu, Xueling Yang, Jia Liu, Huaming Wang, Fan Feng, Zhi Guo
Introduction: Radiofrequency ablation (RFA) is the foremost treatment option for advanced hepatocellular carcinoma (HCC), however, rapid and aggressive recurrence of HCC often occurs after RFA due to epithelial-mesenchymal transition process. Although combination of RFA with sorafenib, a molecular targeted agent, could attenuate the recurrence of HCC, application of this molecular targeted agent poses a heavy medical burden and oral administration of sorafenib also brings severe side effects...
2018: OncoTargets and Therapy
Abdulmajeed A Bahman, Mohamed Salah I Abaza, Sarah I Khoushiash, Rajaa J Al-Attiyah
Sorafenib (Nexavar, BAY43‑9006 or Sora) is the first molecular targeted agent that has exhibited significant therapeutic benefits in advanced hepatocellular carcinoma (HCC). However, not all HCC patients respond well to Sora and novel therapeutic strategies to optimize the efficacy of Sora are urgently required. Plant‑based drugs have received increasing attention owing to their excellent chemotherapeutic and chemopreventive activities; they are also well tolerated, non‑toxic, easily available and inexpensive...
June 8, 2018: International Journal of Molecular Medicine
Pavan Tenneti, Mitesh J Board, Hani M Babiker
The standard of care for early hepatobiliary cancers (HBC) includes surgical resection. Liver transplantations or locoregional therapies are beneficial in early hepatocellular carcinoma (HCC) under certain circumstances. Systemic treatments have some benefit in advanced HBC, though long-term prognosis remains poor. We evaluated the role of oncolytic viruses in the treatment of HBCs through a systematic literature review. The recombinant vaccinia virus JX-594 improved median survival in patients with local/metastatic HCC more strongly at high dose than at low dose (14...
June 14, 2018: Immunotherapy
Mohamed Badawi, Jihye Kim, Anees Dauki, Dhruvitkumar Sutaria, Tasneem Motiwala, Ryan Reyes, Nissar Wani, Shamalatha Kolli, Jinmai Jiang, Christopher C Coss, Samson T Jacob, Mitch A Phelps, Thomas D Schmittgen
The mTOR pathway is activated in about 50% of patients with hepatocellular carcinoma (HCC). In an effort to identify new pathways and compounds to treat advanced HCC, we considered the ATP-competitive mTOR inhibitor INK128. ATP-competitive mTOR inhibitors attenuate both mTORC1 and mTORC2. INK128 was evaluated in sorafenib sensitive and insensitive HCC cell lines, CD44low and CD44high HCC and those cell lines with acquired sorafenib resistance. CD44 was significantly increased in Huh7 cells made resistant to sorafenib...
May 25, 2018: Oncotarget
Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo
Purpose: The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). Materials and Methods: This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration: 50 mg to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 mg to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints...
June 13, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Abdulwahab A Alshahrani, Shin Hwang, Gi-Won Song, Deok-Bog Moon, Dong-Hwan Jung, Chul-Soo Ahn, Ki-Hun Kim, Tae-Yong Ha, Gil-Chun Park, Su-Min Ha, Yo-Han Park, Sung-Gyu Lee
Recurrence of hepatocellular carcinoma (HCC) 10 years after liver transplantation (LT) is very rare. Here, we present two cases of peritoneal metastasis of HCC that occurred 10 and 12 years after LT. A 77-year-old male who had undergone deceased-donor LT 10 years earlier showed slow progressive elevation of tumor marker levels over 6 months. Close observation with frequent imaging studies and monthly tumor marker analyses revealed a solitary peritoneal seeding mass. Imaging studies revealed that the mass was highly likely to be metastatic HCC...
May 2018: Annals of Hepato-Biliary-Pancreatic Surgery
Shu-Fu Lin, Jen-Der Lin, Chuen Hsueh, Ting-Chao Chou, Richard J Wong
Activation of cyclin-dependent kinase activity is frequently observed in many human cancers; therefore, cyclin-dependent kinases that promote cell cycle transition and cell proliferation may be potential targets in the treatment of malignancy. The therapeutic effects of roniciclib, a cyclin-dependent kinase inhibitor for papillary and follicular thyroid cancer (designated as well-differentiated thyroid cancer), were investigated in this study. Roniciclib inhibited cell proliferation in two papillary and two follicular thyroid cancer cell lines in a dose-dependent manner...
June 12, 2018: Endocrine-related Cancer
Lei Liu, Xinlu Pang, Wenjin Shang, Hongchang Xie, Yonghua Feng, Guiwen Feng
Although the use of sorafenib appears to increase the survival rate of renal cell carcinoma (RCC) patients, there is also a proportion of patients who exhibit a poor primary response to sorafenib treatment. Therefore, it is critical to elucidate the mechanisms underlying sorafenib resistance and find representative biomarkers for sorafenib treatment in RCC patients. Herein, we identified that a long noncoding RNA GAS5 was downregulated in sorafenib nonresponsive RCCs. GAS5 overexpression conferred sorafenib sensitive to nonresponsive RCC cells, whereas knockdown of GAS5 promoted responsive RCC cells resistant to sorafenib treatment in vitro and in vivo...
June 12, 2018: Cell Cycle
Chigusa Morizane, Makoto Ueno, Masafumi Ikeda, Takuji Okusaka, Hiroshi Ishii, Junji Furuse
Biliary tract cancer, carcinoma of the extrahepatic bile ducts, carcinoma of the gall bladder, ampullary carcinoma and intrahepatic cholangiocarcinoma are often identified at an advanced stage and have poor prognoses. Although effective chemotherapy regimens are needed, their development remains unsatisfactory. From the results of a phase III clinical trial (ABC-02 trial), gemcitabine plus cisplatin is the standard first-line chemotherapeutic regimen for advanced biliary tract cancer. A phase III trial of gemcitabine plus cisplatin vs...
June 11, 2018: Japanese Journal of Clinical Oncology
Katsunori Tatsugami, Mototsugu Oya, Koki Kabu, Hideyuki Akaza
BACKGROUND: The average age of patients diagnosed with renal cell carcinoma (RCC) is increasing, but a limited number of reports have described therapy of tyrosine kinase inhibitor for elderly RCC patients. Hence, we analysed the efficacy and safety of sorafenib in elderly patients aged ≥75 years with advanced RCC. METHODS: Data were extracted from <75-year-old and ≥75-year-old patient groups, matching those demographics considered to affect prognosis. Differences in patients' characteristics, dose modification, adverse events, tumour response, progression-free survival, and renal function (glomerular filtration) were evaluated between the groups...
June 12, 2018: British Journal of Cancer
Chia-Jui Yen, Tae-You Kim, Yin-Hsun Feng, Yee Chao, Deng-Yn Lin, Baek-Yeol Ryoo, Dennis Chin-Lun Huang, David Schnell, Julia Hocke, Arsène-Bienvenu Loembé, Ann-Lii Cheng
Background: Nintedanib is an oral, triple angiokinase inhibitor of vascular endothelial growth factor/platelet-derived growth factor/fibroblast growth factor receptors. This randomized, multicenter, open-label, phase I/II study evaluated the safety, pharmacokinetics, maximum tolerated dose (MTD) in terms of dose-limiting toxicities (DLTs), and efficacy of nintedanib versus sorafenib in Asian patients with unresectable advanced hepatocellular carcinoma (HCC). Patients and Methods: For the phase I portion, patients were stratified into two groups according to their alanine aminotransferase/aspartate aminotransferase (ALT/AST) and Child-Pugh score at baseline...
May 2018: Liver Cancer
Masatoshi Kudo, Yoon-Koo Kang, Joong-Won Park, Shukui Qin, Yoshitaka Inaba, Eric Assenat, Yoshiko Umeyama, Maria José Lechuga, Olga Valota, Yosuke Fujii, Jean-Francois Martini, J Andrew Williams, Shuntaro Obi
Background: An unmet need exists for treatment of patients with advanced hepatocellular carcinoma (HCC) who progress on or are intolerant to sorafenib. A global randomized phase II trial ( No. NCT01210495) of axitinib, a vascular endothelial growth factor receptor 1-3 inhibitor, in combination with best supportive care (BSC) did not prolong overall survival (OS) over placebo/BSC, but showed improved progression-free survival in some patients. Subgroup analyses were conducted to identify potential predictive/prognostic factors...
May 2018: Liver Cancer
Mikhail S Chesnokov, Polina A Khesina, Darya A Shavochkina, Inna F Kustova, Leonid M Dyakov, Olga V Morozova, Nikolai S Mugue, Nikolay E Kudashkin, Ekaterina A Moroz, Yuri I Patyutko, Natalia L Lazarevich
Background: Hepatocellular carcinoma (HCC) is the most common and aggressive type of malignant liver tumor. HCC progression depends significantly on its vascularization and formation of new blood vessels. Vascular endothelial growth factor A (VEGFA) is a crucial regulator of tumor vascularization and components of VEGF-induced cell signaling pathways are important targets of therapeutical drugs that demonstrated the highest efficiency in case of advanced HCC (sorafenib and regorafenib)...
2018: PeerJ
Yuanyuan Wang, Shanhe Wan, Zhonghuang Li, Yu Fu, Guangfa Wang, Jiajie Zhang, Xiaoyun Wu
Aiming to explore novel BRAFV600E and VEGFR-2 dual inhibitors, a series of 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed, synthesized and biologically evaluated in this study. Most of the synthesized 1H-pyrazolo[3,4-d]pyrimidine compounds displayed moderate to high potent activity in both enzymatic and cellular proliferation assays. Among these compounds, 9e, 9g, 9m and 9u showed remarkably high inhibitory activities against both BRAFV600E and VEGFR-2 kinase comparable to positive control Sorafenib...
June 2, 2018: European Journal of Medicinal Chemistry
Man Tong, Noélia Che, Lei Zhou, Steve T Luk, Phillis W Kau, Stella Chai, Elly S Ngan, Chung-Mau Lo, Kwan Man, Jin Ding, Terence K Lee, Stephanie Ma
BACKGROUND & AIMS: Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Sorafenib is the only FDA approved first-line targeted drug for advanced HCC, but its effect on patients' survival gain is limited. Further, patients ultimately present disease progression. A better understanding of causes of sorafenib resistance, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCC...
June 6, 2018: Journal of Hepatology
Fang Wang, Thomas Bank, Gregory Malnassy, Maribel Arteaga, Na Shang, Annika Dalheim, Xianzhong Ding, Scott J Cotler, Mitchell F Denning, Michael I Nishimura, Peter Breslin, Wei Qiu
Hepatocellular carcinoma (HCC) is the fifth most common primary cancer and second largest cause of cancer-related death worldwide. The first-line oral chemotherapeutic agent sorafenib only increases survival in patients with advanced HCC by less than 3 months. Most patients with advanced HCC have shown limited response rates and survival benefits with sorafenib. Although sorafenib is an inhibitor of multiple kinases, including serine/threonine-protein kinase c-Raf, serine/threonine-protein kinase B-Raf, vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and platelet-derived growth factor receptor β, HCC cells are able to escape from sorafenib treatment using other pathways that the drug insufficiently inhibits...
June 2018: Hepatology Communications
Pierre I Karakiewicz, Emanuele Zaffuto, Anil Kapoor, Naveen S Basappa, Georg A Bjarnason, Normand Blais, Rodney H Breau, Christina Canil, Darrel Drachenberg, Sebastien J Hotte, Claudio Jeldres, Michael A S Jewett, Wassim Kassouf, Christian Kollmannsberger, Luke T Lavallée, Ranjena Maloni, Francois Patenaude, Frédéric Pouliot, M Neil Reaume, Robert Sabbagh, Bobby Shayegan, Alan So, Denis Soulières, Simon Tanguay, Lori Wood, Marco Bandini
INTRODUCTION: The Kidney Cancer Research Network of Canada (KCRNC) collaborated to prepare this consensus statement about the use of target agents as adjuvant therapy in patients with non-metastatic renal cell carcinoma (nmRCC) after nephrectomy. We reviewed the published data and performed a meta-analysis of studies that focused on vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). METHODS: A systematic literature search identified seven trials on adjuvant target therapy in nmRCC...
June 2018: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
Andrew X Zhu, Richard S Finn, Julien Edeline, Stephane Cattan, Sadahisa Ogasawara, Daniel Palmer, Chris Verslype, Vittorina Zagonel, Laetitia Fartoux, Arndt Vogel, Debashis Sarker, Gontran Verset, Stephen L Chan, Jennifer Knox, Bruno Daniele, Andrea L Webber, Scot W Ebbinghaus, Junshui Ma, Abby B Siegel, Ann-Lii Cheng, Masatoshi Kudo
BACKGROUND: Immune checkpoint blockade therapy has shown promising results in patients with advanced hepatocellular carcinoma. We aimed to assess the efficacy and safety of pembrolizumab in this patient population. METHODS: KEYNOTE-224 is a non-randomised, multicentre, open-label, phase 2 trial that is set in 47 medical centres and hospitals across ten countries. Eligible patients had pathologically confirmed hepatocellular carcinoma; had previously been treated with sorafenib and were either intolerant to this treatment or showed radiographic progression of their disease after treatment; an Eastern Cooperative Oncology Group performance status of 0-1; adequate organ function, and were Child-Pugh class A...
June 1, 2018: Lancet Oncology
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