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https://www.readbyqxmd.com/read/29673151/tumor-molecular-profiling-for-an-individualized-approach-to-the-treatment-of-hepatocellular-carcinoma-a-patient-case-study
#1
Kristine Posadas, Anita Ankola, Zhaohai Yang, Nelson S Yee
Hepatocellular carcinoma (HCC) is increasing in incidence, and the associated mortality rate remains among the highest. For advanced HCC, sorafenib has been shown to slightly prolong survival, and regorafenib and nivolumab, both recently approved by the United States Food and Drug Administration (FDA), may produce clinical benefits to a limited extent. Systemic chemotherapy has been shown to produce a modest response, but there is no clinically valid biomarker that can be used to predict which patients may benefit...
April 17, 2018: Biomedicines
https://www.readbyqxmd.com/read/29609689/regorafenib-delays-the-proliferation-of-hepatocellular-carcinoma-by-inducing-autophagy
#2
Rui Han, Shixin Li
The aim of the present study was to investigate the effects of regorafenib on hepatocellular carcinoma autophagy, thereby supressing the malignancy of HCC. First, HepG2 and Hep3B cell autophagy was investigated using GFP-LC3 transfection after the treatment of regorafenib. Then, the activation of Akt/mTOR signaling was analyzed using western blot. Our data showed that liver cancer cell autophagy was significantly induced by 20 μM regorafenib using GFP-LC3 transfection. Meanwhile, regorafenib-induced cell death could largely be abolished by 3-MA or CQ treatment, suggesting that regorafenib-induced HepG2 cell death was partially dependent on autophagy...
April 2, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29606345/gene-polymorphisms-in-the-ccl5-ccr5-pathway-as-a-genetic-biomarker-for-outcome-and-hand-foot-skin-reaction-in-metastatic-colorectal-cancer-patients-treated-with-regorafenib
#3
Mitsukuni Suenaga, Marta Schirripa, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Chiara Cremolini, Carlotta Antoniotti, Beatrice Borelli, Tetsuo Mashima, Satoshi Okazaki, Martin D Berger, Yuji Miyamoto, Roel Gopez, Afsaneh Barzi, Sara Lonardi, Toshiharu Yamaguchi, Alfredo Falcone, Fotios Loupakis, Heinz-Josef Lenz
BACKGROUND: The C-C motif chemokine ligand 5/C-C motif chemokine receptor 5 (CCL5/CCR5) pathway has been shown to induce endothelial progenitor cell migration, resulting in increased vascular endothelial growth factor A expression. We hypothesized that genetic polymorphisms in the CCL5/CCR5 pathway predict efficacy and toxicity in patients with metastatic colorectal cancer (mCRC) treated with regorafenib. PATIENTS AND METHODS: We analyzed genomic DNA extracted from 229 tumor samples from 2 different cohorts of patients who received regorafenib: an evaluation cohort of 79 Japanese patients and a validation cohort of 150 Italian patients...
February 27, 2018: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29599312/-in-vitro-elucidation-of-drug-combination-synergy-in-treatment-of-pancreatic-ductal-adenocarcinoma
#4
Kevin T Bush, Amelie Boichard, Igor F Tsigelny
BACKGROUND/AIM: Advances in therapies targeting proteins and pathways affected by genetic alterations has raised the possibility of personalized cancer treatments. MATERIALS AND METHODS: The efficacy of targeting molecular aberrations was determined in the pancreatic ductal adenocarcinoma (PDAC) cell line, CAPAN2. Two mutations were targeted, KRAS (p.G12V) and ABL1 (p.G1060D), and cells were treated with regorafenib and trametinib, individually and in combination...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29576426/a-pilot-study-of-apatinib-as-third-line-treatment-in-patients-with-heavily-treated-metastatic-colorectal-cancer
#5
Lijun Liang, Lei Wang, Panrong Zhu, Youyou Xia, Yun Qiao, Jiang Wu, Wei Zhuang, Jiayan Fei, Yixuan Wen, Xiaodong Jiang
BACKGROUND: Antiangiogenic therapy has shown improved clinical outcome in metastatic colorectal cancer (mCRC). After the failure of standard treatments, regorafenib and TAS-102 would be recommended for patients with mCRC, however, they have not been approved in China during this study period. PATIENTS AND METHODS: This pilot study aimed to assess the efficacy and safety of apatinib, a novel oral inhibitor targeting vascular endothelial growth factor receptor 2, as third-line treatment for patients with mCRC refractory to standard therapies...
March 2, 2018: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29573334/fgfr2-amplification-is-predictive-of-sensitivity-to-regorafenib-in-gastric-and-colorectal-cancers-in-vitro
#6
Yongjun Cha, Hwang-Phill Kim, Yoojoo Lim, Sae-Won Han, Sang-Hyun Song, Tae-You Kim
Although regorafenib has demonstrated survival benefits in patients with metastatic colorectal and gastrointestinal stromal tumors, no proven biomarker has been identified for predicting sensitivity to regorafenib. Here, we investigated preclinical activity of regorafenib in gastric and colorectal cancer cells to identify genetic alterations associated with sensitivity to regorafenib. Mutation profiles and copy number assays of regorafenib target molecules indicated that amplification of FGFR2 was the only genetic alteration associated with in vitro sensitivity to regorafenib...
March 24, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29569657/regorafenib-for-the-treatment-of-hepatocellular-carcinoma
#7
F Tovoli, A Granito, S De Lorenzo, L Bolondi
Hepatocellular carcinoma (HCC) is a worldwide problem, with a high prevalence in nonindustrialized countries and a rising incidence in industrialized countries as well. Its close association with chronic liver diseases and liver cirrhosis represents a significant challenge in its treatment. A front-line systemic treatment for unresectable cases of HCC (sorafenib) was identified only in 2007. Following a decade of failed clinical trials with a wide range of drugs for second-line treatment, regorafenib proved its efficacy as a second-line treatment in 2016, when the randomized, placebo-controlled, phase III RESORCE trial demonstrated a meaningful increase in overall survival in the regorafenib treatment arm compared with the placebo arm (10...
January 2018: Drugs of Today
https://www.readbyqxmd.com/read/29569472/regorafenib-in-the-treatment-of-metastatic-colorectal-cancer
#8
Christelle de la Fouchardière
Regorafenib is an orally available multikinase inhibitor, currently approved in metastatic chemorefractory colorectal cancer patients. The results of two large randomized Phase III trials are available, providing significant results in overall and progression-free survival in this situation. Its use requires a special attention regarding patient selection, dosing schedule and management of adverse events. Identifying patients who will tolerate and have benefit from regorafenib is a challenge for clinicians...
March 23, 2018: Future Oncology
https://www.readbyqxmd.com/read/29563833/evolution-of-regorafenib-from-bench-to-bedside-in-colorectal-cancer-is-it-an-attractive-option-or-merely-a-me-too-drug
#9
REVIEW
Gaurav Goel
Colorectal cancer (CRC) is a major public health problem in the United States with an estimated 50,260 deaths in 2017. Over the past two decades, several agents have been approved by the US Food and Drug Administration (FDA) for the treatment of patients with metastatic CRC (mCRC). Regorafenib (BAY 73-4506) is a small-molecule multikinase inhibitor that was approved for the treatment of mCRC in 2012. This agent is a novel oral diphenylurea-based multikinase inhibitor that is active against several angiogenic receptor tyrosine kinases (RTKs; VEGFR-1, VEGFR-2, VEGFR-3, TIE-2), oncogenic RTKs (c-KIT, RET), stromal RTKs (PDGFR-B, FGFR-1), and intracellular signaling kinases (c-RAF/RAF-1, BRAF, BRAFV600E )...
2018: Cancer Management and Research
https://www.readbyqxmd.com/read/29552663/micromanagement-of-drug-resistant-advanced-gastrointestinal-stromal-tumors-regorafenib-new-ammunition-in-battling-exon-17-mutations
#10
EDITORIAL
Alexander J Eckardt, Ortwin Klein
No abstract text is available yet for this article.
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29548772/efficacy-and-safety-of-regorafenib-with-2-1-schedule-for-patients-%C3%A2-75-years-with-metastatic-colorectal-cancer-mcrc-after-failure-of-2-lines-of-chemotherapy
#11
Roberto Petrioli, Martina Chirra, Luciana Messuti, Anna Ida Fiaschi, Vinno Savelli, Ignazio Martellucci, Edoardo Francini
BACKGROUND: In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC...
February 21, 2018: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29544202/quantification-of-the-next-generation-oral-anti-tumor-drugs-dabrafenib-trametinib-vemurafenib-cobimetinib-pazopanib-regorafenib-and-two-metabolites-in-human-plasma-by-liquid-chromatography-tandem-mass-spectrometry
#12
Evelina Cardoso, Thomas Mercier, Anna Dorothea Wagner, Krisztian Homicsko, Olivier Michielin, Kim Ellefsen-Lavoie, Laurène Cagnon, Manuel Diezi, Thierry Buclin, Nicolas Widmer, Chantal Csajka, Laurent Decosterd
A sensitive and selective method of high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS) has been developed for the simultaneous quantification of six anticancer protein kinase inhibitors (PKIs), dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib, and two active metabolites (regorafenib-M2 and regorafenib-M5) in human plasma. Plasma protein precipitation with methanol enables the sample extraction of 100 μL aliquot of plasma. Analytes are detected by electrospray triple-stage quadrupole mass spectrometry and quantified using the calibration curves with stable isotope-labeled internal standards...
February 8, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29535278/regorafenib-inhibits-tumor-progression-through-suppression-of-erk-nf-%C3%AE%C2%BAb-activation-in-hepatocellular-carcinoma-bearing-mice
#13
Mao-Chi Weng, Mei-Hui Wang, Jai-Jen Tsai, Yu-Cheng Kuo, Yu-Chang Liu, Fei-Ting Hsu, Hsin-Ell Wang
Regorafenib has been demonstrated in our previous study to trigger apoptosis through suppression of extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) activation in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro However, the effect of regorafenib on NF-κB-modulated tumor progression in HCC in vivo is ambiguous. The aim of the present study is to investigate the effect of regorafenib on NF-κB-modulated tumor progression in HCC bearing mouse model. pGL4.50 luciferase reporter vector transfected SK-Hep1 (SK-Hep1/ luc2 ) and Hep3B 2...
March 13, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29514163/prophylactic-effect-of-dexamethasone-on-regorafenib-related-fatigue-and-or-malaise-a-randomized-placebo-controlled-double-blind-clinical-study-in-patients-with-unresectable-metastatic-colorectal-cancer-kscc1402-hgcsg1402
#14
Hiroaki Tanioka, Yuji Miyamoto, Akihito Tsuji, Masako Asayama, Takeshi Shiraishi, Satoshi Yuki, Masahito Kotaka, Akitaka Makiyama, Mototsugu Shimokawa, Takayuki Shimose, Satohiro Masuda, Takuhiro Yamaguchi, Yoshito Komatsu, Hiroshi Saeki, Yasunori Emi, Hideo Baba, Eiji Oki, Yoshihiko Maehara
BACKGROUND: Regorafenib is an oral multikinase inhibitor with a proven survival benefit for metastatic colorectal cancer patients. The KSCC1402/HGCSG1402 study investigated the prophylactic effect of oral dexamethasone (DEX) on regorafenib-related fatigue and/or malaise. PATIENTS AND METHODS: Patients who progressed after standard chemotherapy were randomized 1: 1 to a DEX group (2 mg/day; days 1-28) with regorafenib or a placebo group with regorafenib. The primary endpoint was the incidence of fatigue and/or malaise, based on version 4...
March 7, 2018: Oncology
https://www.readbyqxmd.com/read/29510588/current-molecular-targeted-therapies-for-bone-and-soft-tissue-sarcomas
#15
REVIEW
Kenji Nakano, Shunji Takahashi
Systemic treatment options for bone and soft tissue sarcomas remained unchanged until the 2000s. These cancers presented challenges in new drug development partly because of their rarity and heterogeneity. Many new molecular targeting drugs have been tried in the 2010s, and some were approved for bone and soft tissue sarcoma. As one of the first molecular targeted drugs approved for solid malignant tumors, imatinib's approval as a treatment for gastrointestinal stromal tumors (GISTs) has been a great achievement...
March 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29506493/mixed-response-on-regorafenib-treatment-for-gist-gastro-intestinal-stromal-tumor-according-to-18-f-fdg-pet-ct
#16
Donatienne Van Weehaeghe, Olivier Gheysens, Vincent Vandecaveye, Patrick Schöffski, Koen Van Laere, Christophe M Deroose
BACKGROUND: Gastro-intestinal stromal tumors (GISTs) are very rare tumors of the gastro-intestinal tract, originating from the interstitial cells of Cajal or a common cell precursor which both express type III tyrosine kinase receptors. Regorafenib is an oral multi-kinase inhibitor used to treat gastro-intestinal stromal tumors. To our knowledge this is the first case in literature to show the response of regorafenib on PET. CASE PRESENTATION: A 37-year-old male with lower abdominal pain and weight loss was referred to our hospital...
March 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29505843/the-role-of-molecular-enrichment-on-future-therapies-in-hepatocellular-carcinoma
#17
REVIEW
Jean-Charles Nault, Peter R Galle, Jens U Marquardt
Hepatocellular carcinomas (HCC) are characterized by considerable phenotypic and molecular heterogeneity. Treatment and design of clinical trials are particularly challenging due a co-existing liver disease present in the majority of patients which limits aggressive therapeutic options. Despite positive results in recent phase III clinical trials, that confirmed the high value of antiangiogenic therapies for HCC in both first (sorafenib and lenvatinib) and second line (regorafenib and cabozantinib) treatment modalities, failure of several large randomized controlled clinical trials over the last 10 years underlines the necessity for innovative treatment strategies and implementation of findings from translational studies to overcome this unmet clinical need...
March 2, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29483433/-a-case-of-metastatic-colorectal-cancer-with-brain-metastasis-treated-with-combined-tftd-and-bevacizumab-therapy
#18
Jin Takano, Nobuhisa Matsuhashi, Takao Takahashi, Toshiyuki Tanahashi, Satoshi Matsui, Hisashi Imai, Yoshihiro Tanaka, Kazuya Yamaguchi, Kazuhiro Yoshida
A woman in her 70s was confirmed as presenting with multiple liver and lung metastases from transverse colon cancer. After undergoing resection of the primary lesion, partial response(PR)was achieved after undergoing the first regimen (sLV5FU2 and bevacizumab[Bmab]); therefore, partial hepatectomy was performed. Adjuvant chemotherapy was administered for 7 months, but liver metastasis recurrence, multiple lung metastases, and brain metastasis were confirmed. As the brain metastasis was a single lesion and was accompanied by symptoms, resection of the lesion was performed...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29465445/regorafenib-associated-fatigue-a-systematic-review-and-meta-analysis
#19
Mihir Invally, Raju Kanukula, M Abdul Salam, Ganta Shruthi
No abstract text is available yet for this article.
February 20, 2018: American Journal of Therapeutics
https://www.readbyqxmd.com/read/29455269/the-efficacy-and-safety-of-targeted-therapy-with-or-without-chemotherapy-in-advanced-gastric-cancer-treatment-a-network-meta-analysis-of-well-designed-randomized-controlled-trials
#20
REVIEW
Ting-Ting Zhao, Hao Xu, Hui-Mian Xu, Zhen-Ning Wang, Ying-Ying Xu, Yong-Xi Song, Song-Cheng Yin, Xing-Yu Liu, Zhi-Feng Miao
BACKGROUND: Advanced gastric cancer (AGC) is a severe malignant tumor associated with high mortality. Targeted therapy is an important approach for improving the therapeutic effects of AGC treatment. This study evaluates the efficacy and safety of targeted agents for AGC patients. METHODS: PubMed, EmBase, and the Cochrane Library were searched for double-blind randomized controlled trials (RCTs) of AGC treatments published prior to July 2017. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and severe adverse effects (AEs) were evaluated to determine the efficacy and safety of targeted agents...
February 17, 2018: Gastric Cancer
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