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https://www.readbyqxmd.com/read/28723497/pharmacogenomic-markers-of-targeted-therapy-toxicity-in-patients-with-metastatic-renal-cell-carcinoma
#1
Guillermo de Velasco, Kathryn P Gray, Lana Hamieh, Yuksel Urun, Hallie A Carol, Andre P Fay, Sabina Signoretti, David J Kwiatkowski, David F McDermott, Matthew Freedman, Mark M Pomerantz, Toni K Choueiri
BACKGROUND: Targeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity. OBJECTIVE: To investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs)...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28714357/pharmaceutical-assistance-programs-for-cancer-patients-in-the-era-of-orally-administered-chemotherapeutics
#2
Aaron Mitchell, Benyam Muluneh, Rachana Patel, Ethan Basch
Introduction The rising cost of cancer drugs may make treatment unaffordable for some patients. Patients often rely on drug manufacturer-administered Pharmaceutical Assistance Programs (PAPs) to obtain drugs and reduced or no cost. The overall usage of PAPs within cancer care delivery is unknown. Methods We included all cancer patients across an academically affiliated, integrated health system in North Carolina during 2014 ( N = 8591). We identified the subset of patients receiving PAP assistance to afford one or more cancer drugs, in order to calculate the proportion of patients receiving PAP assistance, and the retail value of the assistance...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28694417/-a-case-report-metastatic-carcinoma-of-the-collecting-ducts-of-bellini-in-a-hemodialysis-patient-treated-with-temsirolimus
#3
Mizuho Akahane, Masakazu Nakashima, Hiromasa Sakamoto, Teruyoshi Aoyama, Jun Kawai
Carcinoma of the collecting ductsof Bellini isa rare histological subtype of renal cell carcinoma and mostly has unfavorable prognosis. Radical nephrectomy is generally chosen for the 1st line treatment but therapeutic approaches for the metastasis/recurrence have not been established. We report a case of carcinoma of collecting ducts of Bellini in a patient receiving hemodialysis treated with temsirolimus. A 62- year-old man receiving hemodialysis was admitted to our hospital with drug-resistant anemia and high-grade cyclic fever...
June 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28693022/temsirolimus-sensitive-stimulation-of-platelet-activity-apoptosis-and-aggregation-by-collagen-related-peptide
#4
Hang Cao, Rosi Bissinger, Anja T Umbach, Meinrad Gawaz, Florian Lang
BACKGROUND/AIMS: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus stimulates apoptosis of tumor cells and is thus therapeutically used for the treatment of diverse malignancies. On the other hand, temsirolimus has been shown to protect against apoptosis of hippocampal neurons. Similar to nucleated cells, blood platelets may enter suicidal death characterized by cell shrinkage and cell membrane scrambling. Platelet apoptosis is frequently preceded by Ca2+ entry, degranulation, integrin activation and stimulation of caspases...
July 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28676972/erratum-to-a-phase-i-dose-escalation-study-of-selumetinib-in-combination-with-erlotinib-or-temsirolimus-in-patients-with-advanced-solid-tumors
#5
Jeffrey R Infante, Roger B Cohen, Kevin B Kim, Howard A Burris, Gregory Curt, Ugochi Emeribe, Delyth Clemett, Helen K Tomkinson, Patricia M LoRusso
No abstract text is available yet for this article.
July 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28676933/association-of-nr1i2-cyp3a5-and-abcb1-genetic-polymorphisms-with-variability-of-temsirolimus-pharmacokinetics-and-toxicity-in-patients-with-metastatic-bladder-cancer
#6
Litaty C Mbatchi, Matthieu Gassiot, Philippe Pourquier, Alejando Goberna, Hakim Mahammedi, Loic Mourey, Florence Joly, Serge Lumbroso, Alexandre Evrard, Nadine Houede
PURPOSE: Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor that exhibits antitumor activity in renal cell carcinoma and mantle cell lymphoma. The metabolism of temsirolimus and its active metabolite sirolimus mainly depends on cytochrome P450 3A4/5 (CYP3A4/A5) and the ABCB1 transporter. Differently from sirolimus, no pharmacogenetic study on temsirolimus has been conducted. Therefore, the aim of this pilot study was to identify genetic determinants of the inter-individual variability in temsirolimus pharmacokinetics and toxicity...
July 4, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28662274/phase-2-study-evaluating-the-combination-of-sorafenib-and-temsirolimus-in-the-treatment-of-radioactive-iodine-refractory-thyroid-cancer
#7
Eric J Sherman, Lara A Dunn, Alan L Ho, Shrujal S Baxi, Ronald A Ghossein, Matthew G Fury, Sofia Haque, Cami S Sima, Grace Cullen, James A Fagin, David G Pfister
BACKGROUND: Patients with recurrent and/or metastatic, radioactive iodine-refractory thyroid carcinoma have limited treatment options. Sorafenib, an oral kinase inhibitor, is approved by the US Food and Drug Administration for the treatment of radioactive iodine-refractory thyroid carcinoma, although it demonstrated low response rates (12.2%) as a single agent in the first-line setting. The objective of the current study was to determine whether adding the mammalian target of rapamycin inhibitor temsirolimus to sorafenib could improve on these results...
June 29, 2017: Cancer
https://www.readbyqxmd.com/read/28659338/high-throughput-profiling-of-signaling-networks-identifies-mechanism-based-combination-therapy-to-eliminate-microenvironmental-resistance-in-acute-myeloid-leukemia
#8
Zhihong Zeng, Wenbin Liu, Twee Tsao, YiHua Qiu, Yang Zhao, Ismael Samudio, Dos D Sarbassov, Steven M Kornblau, Keith A Baggerly, Hagop M Kantarjian, Marina Konopleva, Michael Andreeff
The bone marrow microenvironment is known to provide a survival advantage to residual acute myeloid leukemia cells, possibly contributing to disease recurrence. The mechanisms by which stroma in the microenvironment regulates leukemia survival remain largely unknown. Using reverse phase-protein array technology, we profiled 53 key protein molecules in 11 signaling pathways in 20 primary acute myeloid leukemia samples and two cell lines, aiming to understand stroma-mediated signaling modulation in response to the targeted agents temsirolimus (MTOR), ABT737 (BCL2/BCL-XL), and Nutlin-3a (MDM2), and to identify the effective combination therapy targeting acute myeloid leukemia in the context of the leukemia microenvironment...
June 28, 2017: Haematologica
https://www.readbyqxmd.com/read/28631253/portal-branch-ligation-does-not-counteract-the-inhibiting-effect-of-temsirolimus-on-extrahepatic-colorectal-metastatic-growth
#9
Sebastian Senger, Jens Sperling, Barbara Oberkircher, Martin K Schilling, Otto Kollmar, Michael D Menger, Christian Ziemann
The mTor-inhibitor temsirolimus (TEM) has potent anti-tumor activities on extrahepatic colorectal metastases. Treatment of patients with advanced disease may require portal branch ligation (PBL). While PBL can induce intrahepatic tumor growth, the effect of PBL on extrahepatic metastases under TEM treatment is unknown. Therefore, we analyzed the effects of TEM treatment on extrahepatic metastases during PBL-associated liver regeneration. GFP-transfected CT26.WT colorectal cancer cells were implanted into the dorsal skinfold chamber of BALB/c-mice...
June 19, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28618305/phase-i-study-of-temsirolimus-in-combination-with-cetuximab-in-patients-with-advanced-solid-tumours
#10
A Hollebecque, R Bahleda, L Faivre, J Adam, V Poinsignon, A Paci, C Gomez-Roca, J C Thery, M C Le Deley, A Varga, A Gazzah, E Ileana, M Gharib, E Angevin, K Malekzadeh, C Massard, J C Soria, J P Spano
BACKGROUND: Preclinical studies suggest synergistic antitumour effects of mammalian target of rapamycin (mTOR) inhibitor such as temsirolimus combined with anti-EGFR monoclonal antibody such as cetuximab. METHODS: Temsirolimus (T) and cetuximab (C) were combined and escalated in cohorts of patients with advanced or metastatic solid tumours, respectively from 15 to 25 mg and 150-250 mg/m(2), until the maximum tolerated dose (MTD) was determined. Effort was made in the expansion cohort to enrol patients harbouring a molecular aberration in the human epidermal growth factor receptor (EGFR) and/or phosphoinositide 3-kinase (PI3K) pathways...
August 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28590313/current-management-of-metastatic-renal-cell-carcinoma-evolving-new-therapies
#11
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/28572534/contrast-media-enhancement-reduction-predicts-tumor-response-to-presurgical-molecular-targeting-therapy-in-patients-with-advanced-renal-cell-carcinoma
#12
Shogo Hosogoe, Shingo Hatakeyama, Ayumu Kusaka, Itsuto Hamano, Yoshimi Tanaka, Kazuhisa Hagiwara, Hideaki Hirai, Satoko Morohashi, Hiroshi Kijima, Hayato Yamamoto, Yuki Tobisawa, Tohru Yoneyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
BACKGROUND AND OBJECTIVE: A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy. RESULTS: Of 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1)...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28561652/evolving-treatment-paradigm-in-metastatic-renal-cell-carcinoma
#13
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/28556689/health-related-quality-of-life-data-from-a-phase-3-international-randomized-open-label-multicenter-study-in-patients-with-previously-treated-mantle-cell-lymphoma-treated-with-ibrutinib-versus-temsirolimus
#14
Georg Hess, Simon Rule, Wojciech Jurczak, Mats Jerkeman, Rodrigo Santucci Silva, Chiara Rusconi, Dolores Caballero, Cristina Joao, Mathias Witzens-Harig, Isabelle Bence-Bruckler, Seok-Goo Cho, Wenjiong Zhou, Jenna D Goldberg, Cristina Trambitas, Christopher Enny, Jessica Vermeulen, Shana Traina, Chiun-Fang Chiou, Joris Diels, Martin Dreyling
Mantle cell lymphoma (MCL) is a rare, aggressive, incurable B-cell malignancy. Ibrutinib has been shown to be highly active for patients with relapsed/refractory (R/R) MCL. The RAY trial (MCL3001) was a phase 3, randomized, open-label, multicenter study that compared ibrutinib with temsirolimus in patients with R/R MCL. Active disease is frequently associated with impaired functional status and reduced well-being. Therefore, the current study employed two patient-reported outcome instruments, the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and the EQ-5D-5L, to assess symptoms, well-being, health status, and health-related quality of life of patients on treatment within the RAY trial...
May 30, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28549783/irinotecan-temozolomide-with-temsirolimus-or-dinutuximab-in-children-with-refractory-or-relapsed-neuroblastoma-cog-anbl1221-an-open-label-randomised-phase-2-trial
#15
Rajen Mody, Arlene Naranjo, Collin Van Ryn, Alice L Yu, Wendy B London, Barry L Shulkin, Marguerite T Parisi, Sabah-E-Noor Servaes, Mitchell B Diccianni, Paul M Sondel, Julia G Bender, John M Maris, Julie R Park, Rochelle Bagatell
BACKGROUND: Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of irinotecan and temozolomide has activity in these patients, and its acceptable toxicity profile makes it an excellent backbone for study of new agents. We aimed to test the addition of temsirolimus or dinutuximab to irinotecan-temozolomide in patients with relapsed or refractory neuroblastoma. METHODS: For this open-label, randomised, phase 2 selection design trial of the Children's Oncology Group (COG; ANBL1221), patients had to have histological verification of neuroblastoma or ganglioneuroblastoma at diagnosis or have tumour cells in bone marrow with increased urinary catecholamine concentrations at diagnosis...
May 23, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28506751/recent-progress-towards-clinically-relevant-atp-competitive-akt-inhibitors
#16
REVIEW
Bayard R Huck, Igor Mochalkin
The frequency of PI3K/Akt/mTOR (PAM) Pathway mutations in human cancers sparked interest to determine if the pathway is druggable. The modest clinical benefit observed with mTOR rapalogs (temsirolimus and everolimus) provided further motivation to identify additional nodes of pathway inhibition that lead to improved clinical benefit. Akt is a central signaling node of the PAM pathway and could be an ideal target for improved pathway inhibition. Furthermore, inhibitors of Akt may be especially beneficial in tumors with Akt1 mutations...
April 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28504837/immunotherapy-for-metastatic-renal-cell-carcinoma
#17
REVIEW
Susanne Unverzagt, Ines Moldenhauer, Monika Nothacker, Dorothea Roßmeißl, Andreas V Hadjinicolaou, Frank Peinemann, Francesco Greco, Barbara Seliger
BACKGROUND: Since the mid-2000s, the field of metastatic renal cell carcinoma (mRCC) has experienced a paradigm shift from non-specific therapy with broad-acting cytokines to specific regimens, which directly target the cancer, the tumour microenvironment, or both.Current guidelines recommend targeted therapies with agents such as sunitinib, pazopanib or temsirolimus (for people with poor prognosis) as the standard of care for first-line treatment of people with mRCC and mention non-specific cytokines as an alternative option for selected patients...
May 15, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28484962/controlled-release-of-second-generation-mtor-inhibitors-to-restrain-inflammation-in-primary-immune-cells
#18
Emily A Gosselin, Lisa H Tostanoski, Christopher M Jewell
Autoimmune disease occurs when the immune system incorrectly targets the body's own tissue. Inflammatory CD4(+) T cell phenotypes, such as TH1 and TH17, are key drivers of this attack. Recent studies demonstrate treatment with rapamycin-a key inhibitor of the mTOR pathway-can skew T cell development, moving T cell responses away from inflammatory phenotypes and toward regulatory T cells (TREGS). TREGS are important in inducing and maintaining tolerance to self-antigens, creating new potential to treat autoimmune diseases more effectively and specifically...
May 8, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28480764/novel-agents-in-mantle-cell-lymphoma
#19
REVIEW
David Tucker, Simon Rule
Mantle cell lymphoma (MCL) usually takes an aggressive clinical course and carries a poor prognosis. Recently, progress has been made in the treatment of MCL including the development of a number of novel agents which target intracellular pathways and the extracellular microenvironment. These agents have transformed the landscape of available therapeutic options. Areas covered: The current literature on the novel agents which currently hold a licence for the treatment of MCL in the context of front-line therapy and in the relapsed/refractory setting is summarized...
June 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28474160/-hereditary-tumor-syndromes-in-neuropathology
#20
REVIEW
C Mawrin
Neoplasms in the central (CNS) and peripheral nervous system (PNS) in hereditary tumor syndromes play an important role in the neuropathological diagnostics. The benign and malignant PNS and CNS tumors that occur in the frequent neurofibromatosis type 1 (NF1) and type 2 (NF2) often represent essential factors for the course of the disease in those affected. Furthermore, certain clinical constellations (e.g. bilateral schwannomas of the auditory nerve, schwannomas at a young age and multiple meningiomas) can be important indications for a previously undiagnosed hereditary tumor disease...
May 4, 2017: Der Pathologe
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