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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
#1
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/28717217/tki-addicted-ros1-rearranged-cells-are-destined-to-survival-or-death-by-the-intensity-of-ros1-kinase-activity
#2
Hayato Ogura, Yuka Nagatake-Kobayashi, Jun Adachi, Takeshi Tomonaga, Naoya Fujita, Ryohei Katayama
ROS1 rearrangement is observed in 1-2% of non-small cell lung cancers (NSCLC). The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has induced marked tumour shrinkage in ROS1-rearranged cancers. However, emergence of acquired resistance to TKI is inevitable within a few years. Previous findings indicate that cabozantinib overcomes secondary mutation-mediated crizotinib-resistance in ROS1-fusion-positive cells. Here we attempted to establish cabozantinib-resistant cells by N-ethyl-N-nitrosourea mutagenesis screening using CD74-ROS1-expressing Ba/F3 cells...
July 17, 2017: Scientific Reports
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
#3
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
#4
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/28698200/targeting-axl-and-mtor-pathway-overcomes-primary-and-acquired-resistance-to-wee1-inhibition-in-small-cell-lung-cancer
#5
Triparna Sen, Pan Tong, Lixia Diao, Lerong Li, Youhong Fan, Jennifer Hoff, John Heymach, Jing Wang, Lauren A Byers
Purpose: Drugs targeting DNA repair and cell cycle checkpoints have emerged as promising therapies for small cell lung cancer (SCLC). Among these, the WEE1 inhibitor AZD1775 has shown clinical activity in a subset of SCLC patients, but resistance is common. Understanding primary and acquired resistance mechanisms will be critical for developing effective WEE1 inhibitor combinations. <p>Experimental Design: AZD1775 sensitivity in SCLC cell lines was correlated with baseline expression level of 200 total or phosphorylated proteins measured by reverse phase protein array (RPPA) to identify predictive markers of primary resistance...
July 11, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28658345/medullary-thyroid-carcinoma-adverse-events-during-systemic-treatment-risk-benefit-ratio
#6
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/28655794/diffusion-mri-phenotypes-predict-overall-survival-benefitfrom-anti-vegf-monotherapy-in-recurrent-glioblastoma-converging-evidence-from-phase-ii-trials
#7
Benjamin M Ellingson, Elizabeth Gerstner, Marion Smits, Raymond Y Huang, Rivka R Colen, Lauren E Abrey, Dana T Aftab, Gisela M Schwab, Colin Hessel, Robert J Harris, Ararat Chakhoyan, Renske Gahrmann, Whitney B Pope, Kevin Leu, Catalina Raymond, Davis C Woodworth, John F de Groot, Patrick Y Wen, Tracy Batchelor, Martin J van den Bent, Timothy F Cloughesy
Anti-VEGF therapies remain controversial in the treatment of recurrent glioblastoma (GBM). In the current study we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an overall survival (OS) advantage when treated with cediranib, bevacizumab, cabozantinib, or aflibercept monotherapy at first or second recurrence. These findings were validated using a separate trial comparing bevacizumab with lomustine. <br /><br />Experimental Design: Patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate Phase II clinical trials were included: 1) cediranib (NCT00035656); 2) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); 3) cabozantinib (XL184-201; NCT00704288); 4) aflibercept (VEGF Trap; NCT00369590); and 5) bevacizumab or lomustine (BELOB; NTR1929)...
June 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28651979/discovery-of-a-highly-potent-selective-and-novel-cdk9-inhibitor-as-an-anticancer-drug-candidate
#8
Yongtao Li, Qingxiang Guo, Chao Zhang, Zhi Huang, Tianqi Wang, Xin Wang, Xiang Wang, Guangwei Xu, Yanhua Liu, Shengyong Yang, Yan Fan, Rong Xiang
A series of novel hybrid structure derivatives, containing both LEE011 and Cabozantinib pharmacophore, were designed, synthesized and evaluated. Surprisingly, a compound 4d was discovered that highly exhibited effective and selective activity of CDK9 inhibition with IC50=12nM. It effectively induced apoptosis in breast and lung cancer cell lines at nanomolar level. Molecular docking of 4d to ATP binding site of CDK9 kinase demonstrated a new hydrogen bonding between F atom of 4-(3-fluorobenzyloxy) group and ASN116 residue, compared with the positive control, LEE011...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28650002/cabozantinib-use-in-renal-cell-carcinoma
#9
A J Neuwelt, S Mathur, A T Johnson, E R Kessler, D W Bowles
In the last several years, many new drugs have been approved to treat metastatic renal cell carcinoma (RCC). Cabozantinib is a novel multikinase inhibitor with activity against vascular endothelial growth factor receptor (VEGFR), proto-oncogene tyrosine-protein kinase receptor Ret and other kinases that recently joined this impressive list of approved agents. Cabozantinib is an active agent in the preclinical and clinical setting, having recently demonstrated superiority over everolimus in a blinded, randomized phase III study of patients with progressive RCC after at least one prior line of antiangiogenic therapy...
May 2017: Drugs of Today
https://www.readbyqxmd.com/read/28634649/assessment-of-cabozantinib-treatment-on-qt-interval-in-a-phase-3-study-in-medullary-thyroid-cancer-evaluation-of-indirect-qt-effects-mediated-through-treatment-induced-changes-in-serum-electrolytes
#10
Dale R Miles, Steven A Lacy, David R Wada, Steve Milwee, Yifah Yaron, Linh T Nguyen
PURPOSE: This study evaluated factors impacting QTc interval in a phase 3 trial of cabozantinib in progressive, metastatic, medullary thyroid cancer (MTC). METHODS: Electrocardiogram (12-lead ECG) measurements were obtained at screening, and at pre-dose, and 2, 4, and 6 h post-dose on Days 1 and 29 in a phase 3 study in patients with MTC treated with cabozantinib (140 mg/day). Central tendency analyses were conducted on baseline-corrected QTc values. Linear and nonlinear mixed-effects models were used to evaluate potential factors affecting the QTc interval, including serum electrolytes, patient demographics, and cabozantinib concentration...
June 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28633552/cabozantinib-for-the-treatment-of-kidney-cancer
#11
REVIEW
Ahmed Abdelaziz, Ulka Vaishampayan
Cabozantinib is a small molecule tyrosine kinase inhibitor that initially showed activity in medullary thyroid cancer and was recently approved by the Food and Drug Administration for the treatment of metastatic renal cell carcinoma after progression on first line therapy. Areas covered: In the METEOR trial, cabozantinib demonstrated significantly improved efficacy in all three endpoints; response rates, progression free survival and overall survival in a randomized trial with everolimus as an active comparator...
July 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28602103/advances-in-small-molecule-therapy-for-treating-metastatic-thyroid-cancer
#12
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/28599410/resistance-to-nanoparticle-albumin-bound-paclitaxel-is-mediated-by-abcb1-in-urothelial-cancer-cells
#13
Stefan Vallo, Raoul Köpp, Martin Michaelis, Florian Rothweiler, Georg Bartsch, Maximilian P Brandt, Kilian M Gust, Felix Wezel, Roman A Blaheta, Axel Haferkamp, Jindrich Cinatl
Nanoparticle albumin-bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro-apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5'-triphosphate-binding cassette transporter subfamily B, member 1 (ABCB1)...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28590313/current-management-of-metastatic-renal-cell-carcinoma-evolving-new-therapies
#14
Ravi Kumar, Anil Kapoor
PURPOSE OF REVIEW: Targeted therapies have recently replaced cytokine treatments as the gold standard for management of metastatic renal cell carcinoma (mRCC). Currently approved treatments include the tyrosine kinase inhibitors sunitinib, pazopanib, axitinib, sorafenib, cabozantinib and lenvatinib; the vascular endothelial growth factor (VEGF) inhibitor bevacizumab; the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus; and the immunologic nivolumab. The purpose of this review is to provide an updated analysis of the clinical data supporting the use of these agents in the first-line and second-line setting...
June 5, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28575860/in-vitro-and-in-vivo-anti-tumor-activity-of-alectinib-in-tumor-cells-with-ncoa4-ret
#15
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/28561652/evolving-treatment-paradigm-in-metastatic-renal-cell-carcinoma
#16
David M Gill, Neeraj Agarwal, Ulka Vaishampayan
The treatment paradigm for advanced and metastatic renal cell carcinoma (mRCC) has evolved rapidly since the arrival of targeted therapies and novel immunotherapies. mRCC was previously treated only with cytokines. However, discoveries of mutations affecting the von Hippel-Lindau tumor suppressor gene (leading to increased expression of VEGF and hypoxia inducible factor/HIF-1) and of deregulations in the phosphatidylinositol-3 kinase/AKT/mTOR pathway (resulting in tumor angiogenesis, cell proliferation, and tumor growth) have led to the development of numerous targeted therapies...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28550387/correlation-of-c-met-expression-with-pd-l1-expression-in-metastatic-clear-cell-renal-cell-carcinoma-treated-by-sunitinib-first-line-therapy
#17
Solène-Florence Kammerer-Jacquet, Sarah Medane, Karim Bensalah, Jean-Christophe Bernhard, Mokrane Yacoub, Frantz Dupuis, Alain Ravaud, Grégory Verhoest, Romain Mathieu, Benoit Peyronnet, Angélique Brunot, Brigitte Laguerre, Alexandra Lespagnol, Jean Mosser, Frédéric Dugay, Marc-Antoine Belaud-Rotureau, Nathalie Rioux-Leclercq
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is highly metastatic. Cabozantinib, an anti-angiogenic tyrosine kinase inhibitor that targets c-MET, provided interesting results in metastatic ccRCC treatment. OBJECTIVE: To understand better the role of c-MET in ccRCC, we assessed its status in a population of patients with metastatic ccRCC. PATIENTS AND METHODS: For this purpose, tumor samples were analyzed for c-MET expression by immunohistochemistry (IHC), for c-MET copy number alterations by fluorescence in situ hybridization (FISH), and for c-MET mutations by next generation sequencing (NGS) in a retrospective cohort of 90 primary ccRCC of patients with metastases treated by first-line sunitinib...
May 26, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28549228/is-cabozantinib-really-better-than-sunitinib-as-first-line-treatment-of-metastatic-renal-cell-carcinoma
#18
Sebastiano Buti, Melissa Bersanelli
No abstract text is available yet for this article.
June 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28515249/incorporating-new-systemic-therapies-in-kidney-cancer-treatment
#19
Eric Jonasch
In 2017, pazopanib and sunitinib remain the mainstays of frontline therapy for advanced renal cell carcinoma. Independent review of frontline cabozantinib therapy may alter standard of care for patients at intermediate and poor risk. Multiple agents show a survival advantage in the second-line setting, including nivolumab, cabozantinib, and combination lenvatinib and everolimus. Selection of subsequent therapy will depend on patient disease status, comorbidities, and resource availability.
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28506408/genetics-of-medullary-thyroid-cancer-an-overview
#20
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
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