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Vismodegib

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https://www.readbyqxmd.com/read/28110457/reduced-proliferation-and-colony-formation-of-head-and-neck-squamous-cell-carcinoma-hnscc-after-dual-targeting-of-egfr-and-hedgehog-pathways
#1
Hannes Liebig, Georg Günther, Marlen Kolb, Christian Mozet, Andreas Boehm, Andreas Dietz, Gunnar Wichmann
PURPOSE: The hedgehog signalling pathway (Hh) is frequently active in head and neck squamous cell carcinoma (HNSCC). Overexpressed Hh associates with poor prognosis. The Hh inhibitor vismodegib targets smoothened, and based on molecular data, may prevent resistance to EGFR targeting. METHODS: To elucidate potential roles of vismodegib in HNSCC therapy, its sole effects and those combined with cisplatin, docetaxel, and cetuximab on HNSCC cell lines were assessed by MTT metabolisation and BrdU incorporation...
January 21, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28101025/giant-basal-cell-carcinomas-arising-on-the-bilateral-forearms-of-a-patient-a-case-report-and-review-of-nonsurgical-treatment-options
#2
Sarah Shangraw, Rivka C Stone, Jeong Hee Cho-Vega, Robert S Kirsner
Giant basal cell carcinomas (GBCCs) are large basal cell carcinomas (BCCs; <5 cm) with a greater propensity to invade and metastasize than standard BCCs. The presence of 2 GBCCs in a single individual is rare. We present the case of a 71-year-old Caucasian male with bilateral GBCCs on the dorsal forearms, measuring 130 cm(2) and 24 cm(2), respectively, that developed over a 21-year period. Over this period, the patient treated the tumors with herbal remedies. Histologic evaluation showed a conventional nodular BCC for both tumors...
September 2016: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28063021/hepatotoxicity-with-vismodegib-an-md-anderson-cancer-center-and-research-on-adverse-drug-events-and-reports-project
#3
Beatrice J Edwards, Dennis W Raisch, Smita S Saraykar, Ming Sun, Josh A Hammel, Hai T Tran, Nathaniel Wehr, Rasha Arabyat, Dennis P West
BACKGROUND: On 30 January 2012, the US FDA approved vismodegib (Erivedge(®), Genentech, CA, USA) for the management of both metastatic and locally advanced basal cell carcinoma. OBJECTIVE: Our objective was to identify evidence of hepatotoxicity with vismodegib in the FDA Adverse Event Reporting System (FAERS) in treated patients in two National Cancer Institute Comprehensive Cancer Centers. METHODS: FAERS was searched for reports dated 1 January 2009 through 31 December 2015 using terms including hedgehog pathway and vismodegib and hepatic-related terms such as liver, jaundice, and hepatitis, among others...
January 6, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28002101/development-of-basal-cell-carcinoma-with-squamous-differentiation-during-vismodegib-treatment
#4
Lawrence Feigenbaum, Brian L Scott, Molly S Moye, Rajiv I Nijhawan
No abstract text is available yet for this article.
December 19, 2016: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28000572/-vismodegib-for-basal-cell-carcinoma-targeted-therapy-in-case-of-locally-advanced-or-metastasised-disease
#5
M G H C Reinders, J B Terra, A K L Reyners, M J Aarts, E R M de Haas, K Mosterd
The development of the hedgehog pathway inhibitor vismodegib provides a new treatment option for metastasised and locally advanced basal cell carcinoma in which surgical excision or radiotherapy is contraindicated. Only a fraction of patients with basal cell carcinoma are eligible for this therapy, but it is effective in the majority of those who do receive vismodegib. However, development of tumour resistance is quite common and adverse events frequently lead to discontinuation of therapy. Intermittent treatment or combination therapy could reduce the occurrence of tumour resistance and diminish toxicity...
2016: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/27972507/cost-efffectivenes-of-sonidegib-versus-vismodegib-for-the-treatment-of-patients-with-locally-advanced-basal-cell-carcinoma-not-amenable-to-surgery-or-radiotherapy
#6
M Purser, D Mladsi, J A Kaye
No abstract text is available yet for this article.
November 2016: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/27942391/metastatic-basal-cell-carcinoma-with-amplification-of-pd-l1-exceptional-response-to-anti-pd1-therapy
#7
Sadakatsu Ikeda, Aaron M Goodman, Philip R Cohen, Taylor J Jensen, Christopher K Ellison, Garrett Frampton, Vincent Miller, Sandip P Patel, Razelle Kurzrock
Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA)...
2016: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/27928965/targeting-the-hedgehog-pathway-for-locally-advanced-and-metastatic-basal-cell-carcinoma
#8
Vivian T Yin, Bita Esmaeli
Basal cell caricnoma (BCC), the most common periocular magliancy, is treated with complete surgical excision. However, in patients not amenable to surgery or when surgical resection means loss of vital organs or disfiguring procedures due to locally advanced or metastatic disease, targeting the hedgehog pathway offers anovel treatment approach for such patients. Mutation in PTCH1 and SMO has been identified in patients with basal cell nevoid syndrome as well as in patients with sporadic BCC. Inhibition of SMO by vismodegib or sonidegib, the two sonic hedgehog inhibitor drugs approved by the Food and Drug Administration in the United States, has shown overall response rate for locally advanced and metastatic BCC around 50%...
December 7, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27906855/periocular-basal-cell-carcinoma-predictors-for-recurrence-and-infiltration-of-the-orbit
#9
Alena Furdova, Pavol Lukacko
PURPOSE: To present the proportion of patients with periocular basal cell carcinoma (BCC) who underwent orbital exenteration and to evaluate the significance of the risk factors. DESIGN: Retrospective, comparative, interventional case series. METHODS: Data of all patients with BCC between 2008 and 2014 were reviewed for patient demographics, previous treatment options, tumor localization, and histopathologic subtype. RESULTS: In group of 256 patients, orbital exenteration underwent 7 patients (2...
November 30, 2016: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/27905158/metastatic-spinal-cord-compression-from-basal-cell-carcinoma-of-the-skin-treated-with-surgical-decompression-and-vismodegib-case-report-and-review-of-hedgehog-signalling-pathway-inhibition-in-advanced-basal-cell-carcinoma
#10
J McGrane, S Carswell, T Talbot
We report a case of a 66-year-old man with locally advanced and metastatic basal cell carcinoma (BCC) causing spinal cord compression, which was treated with spinal surgery and subsequent vismodegib. The patient presented with a large fungating chest wall lesion and a metastasis in T8 that was causing cord compression. He had neurosurgical decompression of the T8 lesion and fixation of the spine. Punch biopsy from the fungating chest wall lesion showed a BCC with some malignant squamous differentiation (basosquamous)...
January 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/27899820/inhibition-of-hedgehog-dependent-tumors-and-cancer-stem-cells-by-a-newly-identified-naturally-occurring-chemotype
#11
Paola Infante, Romina Alfonsi, Cinzia Ingallina, Deborah Quaglio, Francesca Ghirga, Ilaria D'Acquarica, Flavia Bernardi, Laura Di Magno, Gianluca Canettieri, Isabella Screpanti, Alberto Gulino, Bruno Botta, Mattia Mori, Lucia Di Marcotullio
Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the Hh signaling and is a validated target for the development of anticancer compounds, as underlined by the FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) for the treatment of basal cell carcinoma...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27826729/pharmacodynamic-study-of-the-oral-hedgehog-pathway-inhibitor-vismodegib-in-patients-with-metastatic-castration-resistant-prostate-cancer
#12
Benjamin L Maughan, Daniel L Suzman, Brandon Luber, Hao Wang, Stephanie Glavaris, Robert Hughes, Rana Sullivan, Rana Harb, Karim Boudadi, Channing Paller, Mario Eisenberger, Angelo Demarzo, Ashely Ross, Emmanuel S Antonarakis
PURPOSE: Hedgehog (Hh) pathway signaling has been implicated in prostate cancer tumorigenesis and metastatic development and may be upregulated even further in the castration-resistant state. We hypothesized that antagonism of the Hh pathway with vismodegib in men with metastatic castration-resistant prostate cancer (mCRPC) would result in pathway engagement, inhibition and perhaps induce measurable clinical responses in patients. METHODS: This is a single-arm study of oral daily vismodegib in men with mCRPC...
November 8, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27810591/design-synthesis-and-biological-evaluation-of-structurally-modified-isoindolinone-and-quinazolinone-derivatives-as-hedgehog-pathway-inhibitors
#13
Deepak Bhattarai, Joo Hyun Jung, Seunghyeon Han, Hankyu Lee, Soo Jin Oh, Hyuk Wan Ko, Kyeong Lee
The Hedgehog (Hh) signaling pathway is associated with diverse aspects of cellular events, such as cell migration, proliferation, and differentiation throughout embryonic development and tissue patterning. An abnormal Hh signaling pathway is linked to numerous human cancers, including basal cell carcinoma (BCC), medulloblastoma (MB), lung cancer, prostate cancer, and ovarian cancer, and it is therefore a promising target in cancer therapy. Using a structure-hopping approach, we designed new Hh signaling pathway inhibitors with isoindolinone or quinazolinone moieties, which were synthesized and biologically evaluated using an 8xGli-luciferase (Gli-Luc) reporter assay in NIH3T3 cells...
January 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27793816/the-transcription-factor-gli2-as-a-downstream-mediator-of-transforming-growth-factor-%C3%AE-induced-fibroblast-activation-in-ssc
#14
Ruifang Liang, Barbora Šumová, Cinzia Cordazzo, Tatjana Mallano, Yun Zhang, Thomas Wohlfahrt, Clara Dees, Andreas Ramming, Dorota Krasowska, Małgorzata Michalska-Jakubus, Oliver Distler, Georg Schett, Ladislav Šenolt, Jörg H W Distler
OBJECTIVES: Hedgehog signalling plays a critical role during the pathogenesis of fibrosis in systemic sclerosis (SSc). Besides canonical hedgehog signalling with smoothened (SMO)-dependent activation of GLI transcription factors, GLI can be activated independently of classical hedgehog ligands and receptors (so-called non-canonical pathways). Here, we aimed to evaluate the role of non-canonical hedgehog signalling in SSc and to test the efficacy of direct GLI inhibitors that target simultaneously canonical and non-canonical hedgehog pathways...
October 28, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27785832/tumor-regrowth-and-development-of-keratinocytic-neoplasms-in-patients-under-smoothened-inhibition-in-vivo-assessment-with-reflectance-confocal-microscopy
#15
I Alarcon, P Pasquali, J Malvehy, S Puig
BACKGROUND: The regrowth of a tumor after complete clinical response and the development of keratinocytic neoplasms while patients are still undergoing continuous vismodegib have stressed the importance of the accurate monitoring to detect recurrences earlier and ensure the best possible outcome. OBJECTIVE: The objective of this study was to determine the role of reflectance confocal microscopy (RCM) in monitoring the response of locally advanced basal cell carcinoma (laBCC) to vismodegib and to discard secondary resistance...
October 27, 2016: Skin Research and Technology
https://www.readbyqxmd.com/read/27764798/safety-and-efficacy-of-vismodegib-in-patients-aged-%C3%A2-65-years-with-advanced-basal-cell-carcinoma
#16
Anne Lynn S Chang, Karl D Lewis, Sarah T Arron, Michael R Migden, James A Solomon, Simon Yoo, Bann-Mo Day, Edward F McKenna, Aleksandar Sekulic
Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26)...
October 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27732729/study-on-the-risk-of-cutaneous-squamous-cell-carcinoma-after-vismodegib-therapy-for-basal-cell-carcinoma-reply
#17
Shufeng Li, Anne Lynn S Chang
No abstract text is available yet for this article.
October 1, 2016: JAMA Dermatology
https://www.readbyqxmd.com/read/27732728/study-on-the-risk-of-cutaneous-squamous-cell-carcinoma-after-vismodegib-therapy-for-basal-cell-carcinoma-not-a-case-control-study
#18
Susana Puig, Francesca Sampogna, Antonio Tejera-Vaquerizo
No abstract text is available yet for this article.
October 1, 2016: JAMA Dermatology
https://www.readbyqxmd.com/read/27732727/study-on-the-risk-of-cutaneous-squamous-cell-carcinoma-after-vismodegib-therapy-for-basal-cell-carcinoma-not-a-case-control-study
#19
Petter Gjersvik
No abstract text is available yet for this article.
October 1, 2016: JAMA Dermatology
https://www.readbyqxmd.com/read/27694322/hedgehog-pathway-activation-in-t-cell-acute-lymphoblastic-leukemia-predicts-response-to-smo-and-gli1-inhibitors
#20
Antonis Dagklis, Sofie Demeyer, Jolien De Bie, Enrico Radaelli, Daphnie Pauwels, Sandrine Degryse, Olga Gielen, Carmen Vicente, Roel Vandepoel, Ellen Geerdens, Anne Uyttebroeck, Nancy Boeckx, Charles E de Bock, Jan Cools
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive childhood leukemia that is caused by the accumulation of multiple genomic lesions resulting in transcriptional deregulation and increased cell proliferation and survival. Through analysis of gene expression data, we provide evidence that the hedgehog pathway is activated in 20% of T-ALL samples. Hedgehog pathway activation is associated with ectopic expression of the hedgehog ligands Sonic hedgehog (SHH) or Indian hedgehog (IHH), and with upregulation of the transcription factor GLI1 Ectopic expression of SHH or IHH in mouse T cells in vivo caused hedgehog pathway activation in both lymphoid and epithelial cells in the thymus and resulted in increased expression of important T-cell stimulatory ligands (Dll4, Il7, and Vegf) by thymic epithelial cells...
December 8, 2016: Blood
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