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https://www.readbyqxmd.com/read/28911730/management-of-tyrosine-kinase-inhibitors-tki-side-effects-in-differentiated-and-medullary-thyroid-cancer-patients
#1
REVIEW
C Resteghini, S Cavalieri, D Galbiati, R Granata, S Alfieri, C Bergamini, P Bossi, L Licitra, L D Locati
Four tyrosine kinase inhibitors (TKIs) have been recently licensed in thyroid cancer (TC), sorafenib and lenvatinib for differentiated TC, vandetanib and cabozantinib for medullary TC. Others TKIs such as axitinib, pazopanib, sunitinib, have been tested within phase II trials. The toxicity burden associated to TKIs is not negligible. Drug reductions and interruptions are common, definitive drug withdrawals have also been reported as well as toxic deaths in more rare cases. In this context, the prevention of toxicities is mandatory to allow patients to stay on treatment as long as possible without dose and schedule modifications...
June 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28911729/chemotherapy-and-tyrosine-kinase-inhibitors-for-medullary-thyroid-cancer
#2
REVIEW
Julien Hadoux, Martin Schlumberger
Medullary thyroid cancer (MTC) represents 3% of all clinical thyroid cancers and arises from thyroid C cells that produce calcitonin. Locally advanced or metastatic MTC requires a careful work-up including measurement of serum calcitonin and carcinoembryonic antigen, determination of their doubling time and comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for treatment. Cytotoxic chemotherapy can control tumor burden in some patients with response rates of around 20% in old series...
June 2017: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/28860428/-current-status-and-future-perspectives-of-scrum-japan
#3
Atsushi Ohtsu, Koichi Goto, Takayuki Yoshino, Wataru Okamoto, Katsuya Tsuchihara
SCRUM-Japan was launched as a nation-wide genome screening consortium for recruiting patients to 35 sponsor-/investigator- initiated registration trials in collaboration with 15 pharmaceutical companies and 240 hospitals. During the first period between February 2015 and March 2017, a total of 4,805 patients have been enrolled. Genomic profiling of each cancer were analyzed and newdrug applications of label expansion are in preparation based on the results of several registration studies including investigator-initiated trial of vandetanib for RET fusion gene positive non-small cell lung cancer...
August 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28851502/overcoming-abc-transporter-mediated-multidrug-resistance-the-dual-role-of-tyrosine-kinase-inhibitors-as-multitargeting-agents
#4
Giovanni Luca Beretta, Giuliana Cassinelli, Marzia Pennati, Valentina Zuco, Laura Gatti
Resistance to conventional and target specific antitumor drugs still remains one of the major cause of treatment failure and patience death. This condition often involves ATP-binding cassette (ABC) transporters that, by pumping the drugs outside from cancer cells, attenuate the potency of chemotherapeutics and negatively impact on the fate of anticancer therapy. In recent years, several tyrosine kinase inhibitors (TKIs) (e.g., imatinib, nilotinib, dasatinib, ponatinib, gefitinib, erlotinib, lapatinib, vandetanib, sunitinib, sorafenib) have been reported to interact with ABC transporters (e...
August 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28843881/biophysical-and-computational-characterization-of-vandetanib-lysozyme-interaction
#5
Md Zahirul Kabir, Nur Aziean Binti Hamzah, Hamidah Ghani, Saharuddin B Mohamad, Zazali Alias, Saad Tayyab
Interaction of an anticancer drug, vandetanib (VDB) with a ligand transporter, lysozyme (LYZ) was explored using multispectroscopic techniques, such as fluorescence, absorption and circular dichroism along with computational analysis. Fluorescence data and absorption results confirmed VDB-LYZ complexation. VDB-induced quenching was characterized as static quenching based on inverse correlation of KSV with temperature as well as kq values. The complex was characterized by the weak binding constant (Ka=4.96-3...
August 18, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28842826/environmental-enrichment-reverses-tyrosine-kinase-inhibitor-mediated-impairment-through-bdnf-trkb-pathway
#6
Harkaitz Bengoetxea, Irantzu Rico-Barrio, Naiara Ortuzar, Ane Murueta-Goyena, José V Lafuente
Exposure to an enriched environment (EE) has neuroprotective benefits and improves recovery from brain injury due to, among other, increased neurotrophic factor expression. Through these neurotrophins, important cortical and hippocampal changes occur. Vandetanib acts as a tyrosine kinase inhibitor of cell receptors, among others, the vascular endothelial growth factor receptor (VEGFR). Our aim was to investigate the effectiveness of EE counteracting cognitive and cellular effects after tyrosine kinase receptor blockade...
August 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28840516/deleterious-effects-of-vegfr2-and-ret-inhibition-in-a-preclinical-model-of-parkinson-s-disease
#7
C Requejo, J A Ruiz-Ortega, H Bengoetxea, S Bulnes, L Ugedo, J V Lafuente
Neurotrophic factors (NTFs) are a promising therapeutic option for Parkinson's disease (PD). They exert their function through tyrosine kinase receptors. Our goal was to assess the effects of administering a selective tyrosine kinase inhibitor (vandetanib) that blocks VEGFR2 and RET receptors in a preclinical model of PD. Rats underwent intrastriatal injections of 6-hydroxydopamine (6-OHDA). Two weeks later, the rats received 30 mg/kg vandetanib or saline orally. The effects were assessed using the rotational behavioral test, tyrosine hydroxylase (TH) immunohistochemistry, and western blot...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28818671/incidence-and-risk-of-cardiotoxicity-in-cancer-patients-treated-with-targeted-therapies
#8
REVIEW
Matteo Santoni, Federico Guerra, Alessandro Conti, Alessandra Lucarelli, Silvia Rinaldi, Laura Belvederesi, Alessandro Capucci, Rossana Berardi
BACKGROUND: Cardiotoxicityis a serious side effect of molecularly targeted agents. The purpose of this study was to evaluate the incidence and Relative Risk (RR) of developing all-grade and high-grade cardiotoxicity in patients with solid tumors receiving targeted agents through a revised meta-analysis of available clinical trials. METHODS: The scientific literature regarding cardiotoxicity was extensively analyzed using MEDLINE, PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL)...
September 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28740542/vandetanib-eluting-radiopaque-beads-in-vivo-pharmacokinetics-safety-and-toxicity-evaluation-following-swine-liver-embolization
#9
Alban Denys, Peter Czuczman, David Grey, Zainab Bascal, Rhys Whomsley, Hugh Kilpatrick, Andrew L Lewis
PURPOSE: To evaluate the plasma and tissue pharmacokinetics, safety and toxicity following intra-arterial hepatic artery administration of Vandetanib (VTB)-eluting Radiopaque Beads (VERB) in healthy swine. MATERIALS AND METHODS: In a first phase, healthy swine were treated with hepatic intra-arterial administration of VERB at target dose loading strengths of 36 mg/mL (VERB36), 72 mg/mL (VERB72) and 120 mg/mL (VERB120). Blood and tissue samples were taken and analysed for VTB and metabolites to determine pharmacokinetic parameters for the different dose forms over 30 days...
2017: Theranostics
https://www.readbyqxmd.com/read/28733794/fatigue-associated-with-newly-approved-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-an-up-to-date-meta-analysis
#10
REVIEW
Jing Li, Jian Gu
The fatigue associated with five newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) is poorly understood. We conducted this systematic review to fully investigate the fatigue associated with these VEGFR-TKIs in cancer patients. Relevant studies of randomized controlled trials in cancer patients treated with the five VEGFR-TKIs were retrieved and a systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until March 2017...
July 21, 2017: International Journal of Clinical Oncology
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
#11
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/28698976/medullary-thyroid-cancer-clinical-characteristics-and-new-insights-into-therapeutic-strategies-targeting-tyrosine-kinases
#12
REVIEW
Sadegh Rajabi, Mehdi Hedayati
Medullary thyroid carcinoma (MTC) is a hyperplasia of thyroid C-cells, accounting for 5-10% of all thyroid cancers. MTCs may appear as sporadic or hereditary forms, and several molecules and signaling pathways have been found to function defectively in MTC cells. Tyrosine kinases are the most well-studied molecules that have abnormal function in these tumor cells. Due to their limited response, chemotherapeutic agents and radiation therapy are not effective in treating patients with advanced metastatic MTC...
July 11, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28658345/medullary-thyroid-carcinoma-adverse-events-during-systemic-treatment-risk-benefit-ratio
#13
Léa Maria Zanini Maciel, Patrícia Künzle Ribeiro Magalhães
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from parafollicular C cells of the thyroid and associated with mutations in the proto-oncogene REarranged during Transfection (RET). The prognosis of MTC depends on clinical stage, with a 95.6% 10-year survival rate among patients with localized disease and 40% among patients with advanced disease. Standard chemotherapy and radiotherapy have no significant impact on the overall survival of these patients and two tyrosine kinase receptor inhibitors (TKIs), vandetanib and cabozantinib, have been recently approved for the systemic treatment of locally advanced or metastatic MTC...
June 26, 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28635560/sorafenib-in-japanese-patients-with-locally-advanced-or-metastatic-medullary-thyroid-carcinoma-and-anaplastic-thyroid-carcinoma
#14
Yasuhiro Ito, Naoyoshi Onoda, Ken-Ichi Ito, Iwao Sugitani, Shunji Takahashi, Iku Yamaguchi, Koki Kabu, Katsuya Tsukada
BACKGROUND: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC...
September 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28602103/advances-in-small-molecule-therapy-for-treating-metastatic-thyroid-cancer
#15
Jolanta Krajewska, Tomasz Gawlik, Barbara Jarzab
Multi kinase inhibitors (MKIs) are new drugs, which show activity against receptors of different growth factors leading to the inhibition of tumor cells growth and proliferation. This review summarizes a 10-year experience with the use of MKIs in thyroid cancer (TC). It focuses not only on sorafenib, lenvatinib, vandetanib and cabozantinib, already approved in TC, but also presents an overview of the results of different trials with distinct MKIs so far carried out in TC. Areas covered: Published results of phase I, II and III studies and other reports evaluated the efficacy of different targeted drugs in TC...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28575860/in-vitro-and-in-vivo-anti-tumor-activity-of-alectinib-in-tumor-cells-with-ncoa4-ret
#16
Sachiko Arai, Kenji Kita, Azusa Tanimoto, Shinji Takeuchi, Koji Fukuda, Hiroshi Sato, Seiji Yano
Rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) accounts for approximately 1-2% of all NSCLCs. To date, RET fusions that involve at least six fusion partners in NSCLC, such as KIF5B, CCDC6, NCOA4, TRIM33, CLIP1, and ERC1, have been identified. Recent clinical trials for RET fusion-positive NSCLC using vandetanib or cabozantinib demonstrated positive clinical response and considerable differential activities for RET inhibitors among fusion partners. Alectinib, an approved ALK inhibitor, is reported to inhibit KIF5B-RET and CCDC6-RET...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28559461/the-hgf-c-met-pathway-is-a-driver-and-biomarker-of-vegfr-inhibitor-resistance-and-vascular-remodeling-in-non-small-cell-lung-cancer
#17
Tina Cascone, Li Xu, Heather Y Lin, Wenbin Liu, Hai T Tran, Yuan Liu, Kathryn Howells, Vincent Haddad, Emer Hanrahan, Monique B Nilsson, Maria A Cortez, Uma Giri, Humam Kadara, Babita Saigal, Yun-Yong Park, Weiyi Peng, Ju-Seog Lee, Anderson J Ryan, Juliane M Jüergensmeier, Roy S Herbst, Jing Wang, Robert R Langley, Ignacio I Wistuba, Jack J Lee, John V Heymach
Purpose: Resistance to VEGFR inhibitors is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). We investigated the cellular mechanisms mediating resistance of NSCLCs to VEGFR tyrosine kinase inhibitors.Experimental Design: We generated murine models of human NSCLC and performed targeted inhibition studies with the VEGFR TKIs cediranib and vandetanib. We used species-specific hybridization of microarrays to compare cancer (human) and stromal (mouse) cell transcriptomes of TKI-sensitive and -resistant tumors...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28506408/genetics-of-medullary-thyroid-cancer-an-overview
#18
REVIEW
Giacomo Accardo, Giovanni Conzo, Daniela Esposito, Claudio Gambardella, Marco Mazzella, Filomena Castaldo, Carlo Di Donna, Andrea Polistena, Nicola Avenia, Vittorio Colantuoni, Dario Giugliano, Daniela Pasquali
Medullary thyroid carcinoma (MTC) represents 3-5% of thyroid cancers. 75% is sporadic and 25% is the dominant component of the hereditary multiple endocrine neoplasia (MEN) type 2 syndromes. Three different subtypes of MEN2, such as MEN2A, MEN2B, and Familial MTC (FMTC) have been defined, based on presence or absence of hyperparathyroidism, pheocromocytoma and characteristic clinical features. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC, but there are many other mutational patterns involved...
May 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28475408/vandetanib-and-cabozantinib-potentiate-mitochondria-targeted-agents-to-suppress-medullary-thyroid-carcinoma-cells
#19
Dmytro Starenki, Seung-Keun Hong, Pui-Kei Wu, Jong-In Park
Although the FDA-approved receptor tyrosine kinases inhibitors, vandetanib and cabozantinib, are used to treat surgically inoperable progressive medullary thyroid carcinoma (MTC), not all patients are responsive while the disease sometimes progresses after an initial response. To better understand MTC drug resistance at molecular and biochemical levels, we have generated drug-resistant subpopulations of the human MTC cell lines, TT and MZ-CRC-1, via prolonged exposure to vandetanib and cabozantinib. These drug-resistant progenies exhibited substantial cross-resistance to vandetanib and cabozantinib, suggesting that these inhibitors may invoke an overlapping resistance mechanism(s) in MTC cells...
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#20
MULTICENTER STUDY
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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