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https://www.readbyqxmd.com/read/28721456/antiangiogenic-tyrosine-kinase-inhibitors-in-colorectal-cancer-is-there-a-path-to-making-them-more-effective
#1
REVIEW
Thomas B Karasic, Mark A Rosen, Peter J O'Dwyer
Antiangiogenic therapy has a proven survival benefit in metastatic colorectal cancer. Inhibition of the VEGF pathway using a variety of extracellular antibody approaches has clear benefit in combination with chemotherapy, while intracellular blockade using tyrosine kinase inhibitors (TKIs) such as sorafenib and regorafenib has had more limited success. Pharmacodynamic modeling using modalities such as DCE-MRI indicates potent antiangiogenic effects of these TKIs, yet numerous combination therapies, primarily with chemotherapy, have failed to demonstrate an additive benefit...
July 18, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28719584/health-policy-me-too-drugs-with-limited-benefits-the-tale-of-regorafenib-for-hcc
#2
Bishal Gyawali, Vinay Prasad
No abstract text is available yet for this article.
July 18, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28712319/primary-liver-cancer-genome-sequencing-translational-implications-and-challenges
#3
Demosthenes E Ziogas, Ioannis D Kyrochristos, Georgios K Glantzounis, Dimitrios Christodoulou, Evangelos Felekouras, Dimitrios H Roukos
The prognosis of primary liver cancer (PLC) remains poor and is explained by the slow progress in understanding the molecular pathways driving tumorigenesis, therapeutic resistance and relapse. For early PLCs, complete surgical resection is the only effective treatment, with sorafenib and, more recently, regorafenib prolonging overall survival by a few months. Areas covered: Application of next-generation sequencing (NGS), including targeted NGS (tNGS), whole-exome sequencing (WES), whole-genome sequencing (WGS) and RNA sequencing (RNAseq), on clinical samples from patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) could aid in comprehending tumorigenesis, genetic and genomic heterogeneity, as well as developing molecular classifications for specialized targeted therapy...
July 17, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28712098/precision-medicine-in-metastatic-colorectal-cancer-relevant-carcinogenic-pathways-and-targets-part-1-biologic-therapies-targeting-the-epidermal-growth-factor-receptor-and-vascular-endothelial-growth-factor
#4
REVIEW
Benjamin A Weinberg, Marion L Hartley, Mohamed E Salem
The survival of patients with metastatic colorectal cancer has improved dramatically in recent years, with overall survival exceeding 3 years in large randomized clinical trials. There are now several treatment options for patients with metastatic colorectal cancer. In addition to chemotherapy backbones utilizing fluoropyrimidine, oxaliplatin, and irinotecan combinations, biologic agents that target specific oncogenic pathways have contributed to the improved survival observed in this patient population. This class of medications includes epidermal growth factor receptor (EGFR)-targeted drugs (cetuximab and panitumumab) and vascular endothelial growth factor (VEGF)-targeted therapies (bevacizumab, ramucirumab, ziv-aflibercept, and regorafenib)...
July 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28710508/risk-of-gastrointestinal-events-with-newly-approved-after-2011-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-a-meta-analysis-of-randomized-controlled-trials
#5
REVIEW
Jing Li, Jian Gu
PURPOSE: We performed a meta-analysis to systematically review the gastrointestinal (GI) events (diarrhea, nausea, vomiting, anorexia) of five newly approved (after 2011) VEGFR-TKIs in cancer patients. METHODS: The relevant studies of the randomized controlled trials (RCTs) in cancer patients treated with cabozantinib, vandetanib, lenvatinib, regorafenib, and axitinib were retrieved and the systematic evaluation was conducted. RESULTS: Forty-one randomized controlled trials and 10,860 patients were included...
July 15, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28693355/postsorafenib-systemic-treatments-for-hepatocellular-carcinoma-questions-and-opportunities-after-the-regorafenib-trial
#6
Francesco Tovoli, Stefania De Lorenzo, Maria Aurelia Barbera, Ingrid Garajova, Giorgio Frega, Andrea Palloni, Maria Abbondanza Pantaleo, Guido Biasco, Giovanni Brandi
The search for systemic therapies for hepatocellular carcinoma has been characterized by difficulties and failures. Despite recent progresses, many issues are still to be settled. In particular, the development of drugs inhibiting different neoplastic pathways remains a priority for patients intolerant or resistant to antiangiogenic drugs. This task may be daunting, as previous failures extensively demonstrated. We aimed to identify the future perspective of postsorafenib trials analyzing the strengths and the critical points of past and currently undergoing studies, in the light of the most recent evidences in the field...
July 11, 2017: Future Oncology
https://www.readbyqxmd.com/read/28693192/regorafenib-diminishes-the-expression-and-secretion-of-angiogenesis-and-metastasis-associated-proteins-and-inhibits-cell-invasion-via-nf-%C3%AE%C2%BAb-inactivation-in-sk-hep1-cells
#7
Yu-Chang Liu, Reng-Hong Wu, Wei-Shu Wang
The aim of the present study was to investigate the effects of regorafenib on the nuclear factor κ-light-chain-enhancer of activated B cells (NF)-κB-modulated expression of angiogenesis- and metastasis-associated proteins and cell invasion in human hepatocellular carcinoma SK-Hep1 cells. The SK-Hep1 cells were treated with different concentrations of NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl) ethyl] quinazoline-4,6-diamine (QNZ) or regorafenib for 24 or 48 h. The effects of QNZ and regorafenib on cell viability, NF-κB activation, expression and secretion levels of angiogenesis- and metastasis-associated proteins and cell invasion were evaluated with MTT assays, western blotting, ELISA, gelatin zymography and cell invasion assays...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28687627/phase-ii-trial-of-sorafenib-in-combination-with-capecitabine-in-patients-with-hepatocellular-carcinoma-inst-08-20
#8
Yehuda Patt, Cristhiam Rojas-Hernandez, Houman Mohammad Fekrazad, Pranshu Bansal, Fa Chyi Lee
LESSONS LEARNED: There continues to be a lack of systemic options for advanced hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the only approved options. There exists a potential to combine sorafenib with chemotherapeutic agents shown to be active in HCC, such as capecitabine, safely.Good tumor response was observed, with objective improvement in a few patients seldom seen by single agent sorafenib; however, because of the limited number of patients, meaningful conclusions on survival cannot be drawn...
July 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28685689/arylurea-derivatives-a-class-of-potential-cancer-targeting-agents
#9
Jia-Nian Chen, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou, Shi-Ming Pu, Wan-Hua Lin
Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), epidermal growth factor receptors (EGFRs), insulin-like growth factor 1 receptor (IGF-1R), Fms-like tyrosine kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include checkpoint kinases (Chks), cyclin-dependent kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include matrix metalloproteinases (MMPs), LIM kinase (Limk), nicotinamide phosphoribosyltransferase (Nampt), and histone deacetylase (HDAC); (6) arylureas from the rational modification of natural products...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28662266/cost-effectiveness-of-regorafenib-as-second-line-therapy-for-patients-with-advanced-hepatocellular-carcinoma
#10
Neehar D Parikh, Amit G Singal, David W Hutton
BACKGROUND: Regorafenib, a multikinase inhibitor, has demonstrated prolonged survival by 2.8 months as a second-line agent in patients with hepatocellular carcinoma (HCC) who progress on sorafenib therapy. The objective of the current study was to examine the cost effectiveness of regorafenib for the treatment of HCC. METHODS: The authors constructed a Markov simulation model of patients with unresectable HCC and Child-Pugh A cirrhosis who received treatment with regorafenib versus best supportive care...
June 29, 2017: Cancer
https://www.readbyqxmd.com/read/28649871/the-potential-role-of-nintedanib-in-treating-colorectal-cancer
#11
Antonio Rossi, Tiziana Pia Latiano, Paola Parente, Cinzia Chiarazzo, Filomena Limosani, Gabriele Di Maggio, Evaristo Maiello
Angiogenesis leads to the growth, progression, and metastases of a variety of solid tumors, including metastatic colorectal cancer (mCRC), involving particularly the family of vascular endothelial growth factors (VEGF) and their receptors (VEGFR). Several anti-angiogenic inhibitors are already registered for mCRC therapy: bevacizumab, aflibercept, ramucirumab, regorafenib. Nintedanib is a new triple angiokinase oral inhibitor that potently blocks the proangiogenic pathways mediated by VEGFR, platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR)...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28636293/-treatment-of-advanced-hepatocellular-carcinoma-novel-agents-and-role-of-local-therapy
#12
Louis Parisod, Rafael Duran, Alban Denys, Antonia Digklia
The incidence of hepatocellular carcinoma (HCC) is increasing in Switzerland and its treatment is a challenge. The purpose of this article is to summarize the different therapeutic approaches in the metastatic stage, as well as the perspectives of targeted treatments and immunotherapy. Until recently, the only recognized therapeutic standard for these patients with metastatic CHC was sorafenib, a tyrosine kinase inhibitor. If the patient was to progress under sorafenib, no other recognized therapeutic option was available as second line...
May 17, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28626729/a-new-era-of-systemic-therapy-for-hepatocellular-carcinoma-with-regorafenib-and-lenvatinib
#13
EDITORIAL
Masatoshi Kudo
No abstract text is available yet for this article.
June 2017: Liver Cancer
https://www.readbyqxmd.com/read/28622036/molecular-targeted-drugs-and-treatment-of-colorectal-cancer-recent-progress-and-future-perspectives
#14
Fang Geng, Zheng Wang, Hang Yin, Junxian Yu, Bangwei Cao
Nowadays, colorectal cancer is the fourth most common type of tumor all over the world. When diagnosed, ∼50%-60% of tumors have metastasized, thus resulting in a grim prognosis. Chemotherapy is regarded as standard treatment for patients with colorectal cancer, however, limitations of chemotherapy cannot be ignored, such as low selectivity, insufficient concentrations in tumor tissues, and systemic toxicity. Recently, six targeted drugs have been approved by the U.S. Food and Drug Administration (FDA) for treatment of metastatic colorectal cancer (mCRC), including bevacizumab, aflibercept, regorafenib, cetuximab, and panitumumab...
June 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28621683/genomic-analysis-of-exceptional-responder-to-regorafenib-in-treatment-refractory-metastatic-rectal-cancer-a-case-report-and-review-of-the-literature
#15
Krittiya Korphaisarn, Jonathan M Loree, Van Nguyen, Ryanne Coulson, Vijaykumar Holla, Beate C Litzenburger, Ken Chen, Gordon B Mills, Dipen M Maru, Funda Meric-Bernstan, Kenna R Mills Shaw, Scott Kopetz
We present the case of a 53-year-old male with metastatic rectal cancer who was treatment resistant to FOLFOX and FOLFOXIRI. Due to a Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, regorafenib was given in the third line setting. Surprisingly, the patient had a prolonged partial response that lasted 27 months. Mutational status was extensively evaluated to identify potential alterations that might play a role as predictive markers for this unusual event. A poorly characterized but nontransforming mutation in Fms-like tyrosine kinase 4 (FLT4) was present in the tumor...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28613123/regorafenib-a-newly-approved-drug-for-advanced-hepatocellular-carcinoma
#16
Ioannis D Kyrochristos, Demosthenes E Ziogas, Dimitrios H Roukos
No abstract text is available yet for this article.
June 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28608276/a-comparison-of-yttrium-90-microsphere-radioembolization-to-hepatic-arterial-infusional-chemotherapy-for-patients-with-chemo-refractory-hepatic-colorectal-metastases
#17
REVIEW
Andrea Cercek, Vyacheslav Gendel, Salma Jabbour, Dirk Moore, Chunxia Chen, John Nosher, Marinela Capanu, Joanne F Chou, Taryn Boucher, Nancy Kemeny, Darren R Carpizo
Patients with unresectable hepatic colorectal metastases who become chemo-refractory have limited treatment options. Systemic chemotherapies such as TAS102 and regorafenib have been used in the refractory setting, but with only modest improvement in overall survival compared to best supportive care. In patients with liver-only or liver-dominant disease, direct chemotherapy to the liver such as hepatic artery infusional (HAI) chemotherapy and radioembolization (yttrium-90 (Y90)) should be considered. Due to the difficulty of HAI therapy post Y90 for technical reasons, we recommend HAI therapy prior to Y90...
July 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28605614/medical-management-of-hepatocellular-carcinoma
#18
Nicole E Rich, Adam C Yopp, Amit G Singal
Hepatocellular carcinoma (HCC) typically occurs in patients with advanced liver disease, so therapeutic decisions must account for the degree of underlying liver dysfunction and patient performance status in addition to tumor burden. Curative treatment options, including liver transplantation, surgical resection, and local ablative therapies, offer 5-year survival rates exceeding 60% but are restricted to patients with early-stage HCC. Surgical resection and local ablative therapies are also limited by high recurrence rates, highlighting a need for adjuvant and/or neoadjuvant therapies...
June 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28604110/emerging-tyrosine-kinase-inhibitors-for-the-treatment-of-hepatocellular-carcinoma
#19
REVIEW
Laure de Rosamel, Jean-Frederic Blanc
Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer in the world and the third leading cause of death. Unfortunately, when diagnosed two thirds of patients have an advanced disease for which only palliative treatment can be proposed and most likely systemic therapy. Areas covered: As of today only one systemic therapy is validated in the treatment of advanced HCC, a tyrosine kinase inhibitor (TKI): Sorafenib. Treatment options are therefore lacking. With the advent of Sorafenib other TKIs have been studied with some disappointing results...
June 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28602170/treatment-options-for-metastatic-colorectal-cancer-in-patients-with-liver-dysfunction-due-to-malignancy
#20
REVIEW
L Faugeras, A Dili, A Druez, B Krug, C Decoster, L D'Hondt
BACKGROUND: The survival of colorectal cancer patients is frequently determined by the extent of metastatic invasion to the liver; in cases of major involvement, therapeutic strategies are limited because the liver is necessary for drug metabolism. MATERIAL AND METHODS: We have reviewed articles about the pharmacokinetic profiles of each drug used in colorectal cancer patients with hepatic dysfunction to determine which of these treatments are most feasible. RESULTS: Some drugs appear to be feasible options for patients with hepatic insufficiency...
July 2017: Critical Reviews in Oncology/hematology
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