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Vismodegib

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https://www.readbyqxmd.com/read/27906855/periocular-basal-cell-carcinoma-predictors-for-recurrence-and-infiltration-of-the-orbit
#1
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
#2
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)...
November 30, 2016: 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
#3
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
#4
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
#5
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...
October 19, 2016: 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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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 SHH or IHH, and with upregulation of the transcription factor GLI1...
September 30, 2016: Blood
https://www.readbyqxmd.com/read/27682250/complete-and-sustained-response-of-adult-medulloblastoma-to-first-line-sonic-hedgehog-inhibition-with-vismodegib
#13
Emil Lou, Matthew Schomaker, Jon D Wilson, Mary Ahrens, Michelle Dolan, Andrew C Nelson
Medulloblastoma is an aggressive primitive neuroectodermal tumor of the cerebellum that is rare in adults. Medulloblastomas fall into 4 prognostically significant molecular subgroups that are best defined by experimental gene expression profiles: the WNT pathway, sonic hedgehog (SHH) pathway, and subgroups 3 and 4 (non-SHH/WNT). Medulloblastoma of adults belong primarily to the SHH category. Vismodegib, an SHH-pathway inhibitor FDA-approved in 2012 for treatment of basal cell carcinoma, has been used successfully in the setting of chemorefractory medulloblastoma, but not as a first-line therapy...
August 12, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27672417/the-use-of-noninvasive-optical-coherence-tomography-to-monitor-the-treatment-progress-of-vismodegib-and-imiquimod-5-cream-in-a-transplant-patient-with-advanced-basal-cell-carcinoma-of-the-nose
#14
Orit Markowitz, Michelle Schwartz
Immunosuppressed transplant recipients have increased risk for the development of basal cell carcinoma skin cancers. While oral vismodegib therapy has been successful in treating locally advanced basal cell tumors, few studies document its use and efficacy in organ transplant patients. In this immunocompromised population, topical imiquimod 5% cream has been shown to be an effective and well-tolerated option for superficial and nodular basal cell carcinomas. To the authors' knowledge, no data documents the use of optical coherence tomography, a noninvasive imaging technique, to monitor progress of such combined therapies on in vivo skin...
August 2016: Journal of Clinical and Aesthetic Dermatology
https://www.readbyqxmd.com/read/27640448/managing-adverse-events-associated-with-vismodegib-in-the-treatment-of-basal-cell-carcinoma
#15
Kate Fife, Robert Herd, Susan Lalondrelle, Ruth Plummer, Amy Strong, Sarah Jones, John T Lear
Basal cell carcinomas are the most common form of skin cancer. Some develop into advanced cases not suitable for standard therapy. Vismodegib is the first-in-class oral hedgehog pathway inhibitor (which is dysregulated in 90% of basal cell carcinomas), and has demonstrated efficacy for advanced disease in clinical trials. An UK expert panel met to discuss management strategies for adverse events associated with vismodegib (most commonly taste disturbances, muscle cramps and alopecia). Managing patient expectations and implementing treatment breaks were considered important strategies...
September 19, 2016: Future Oncology
https://www.readbyqxmd.com/read/27636236/the-safety-and-efficacy-of-sonidegib-for-the-treatment-of-locally-advanced-basal-cell-carcinoma
#16
Nicholas J Collier, Faisal R Ali, John T Lear
INTRODUCTION: Basal cell carcinomas (BCCs) are the commonest malignancy in the Western world. Locally advanced BCCs (laBCCs) represent tumours that have developed in difficult-to-treat facial sites, aggressively recurrent tumours, large neglected tumours and those in which current treatment options are excluded by clinical or patient-driven criteria. It is estimated laBCCs represent 1% of BCCs. AREAS COVERED: Sonidegib is an oral hedgehog pathway inhibitor with a novel structure...
October 2016: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/27581207/safety-and-efficacy-of-vismodegib-in-patients-with-basal-cell-carcinoma-nevus-syndrome-pooled-analysis-of-two-trials
#17
Anne Lynn S Chang, Sarah T Arron, Michael R Migden, James A Solomon, Simon Yoo, Bann-Mo Day, Edward F McKenna, Aleksandar Sekulic
BACKGROUND: Aberrant activation of the Hedgehog (Hh) pathway is a key driver in the pathogenesis of basal cell carcinomas (BCCs), including patients with BCC nevus syndrome (BCCNS). It is unclear whether BCCs arising in patients with BCCNS respond differently to vismodegib than in patients without BCCNS. We examined the best overall response rate (BORR) and adverse events (AEs) of vismodegib in patients with advanced BCC (aBCC) with and without BCCNS. METHODS: Patients were treated with vismodegib 150 mg/day in the ERIVANCE BCC trial (ClinicalTrials...
2016: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/27551002/found-in-translation-maximizing-the-clinical-relevance-of-nonclinical-oncology-studies
#18
Mary E Spilker, Xiaoying Chen, Ravi Visswanathan, Chandra Vage, Shinji Yamazaki, Gang G Li, Judy Lucas, Erica L Bradshaw-Pierce, Paolo Vicini
PURPOSE: The translation of nonclinical oncology studies is a subject of continuous debate. We propose that translational oncology studies need to optimize both pharmacokinetic (drug exposure) and pharmacodynamic (xenograft model) aspects. While improvements in pharmacodynamic translatability can be obtained by choosing cell lines or patient-derived xenograft models closer to the clinical indication, significant ambiguity and variability exists when optimizing the pharmacokinetic translation of small molecule and biotherapeutic agents...
August 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27538055/sonidegib-for-the-treatment-of-advanced-basal-cell-carcinoma
#19
Egle Ramelyte, Valerie C Amann, Reinhard Dummer
INTRODUCTION: Advanced and metastatic basal cell carcinomas (BCCs) are rare but still present a severe medical problem. These tumors are often disfiguring and impact the quality of life by pain or bleeding. Based on discovery of the hedgehog (Hh) signaling pathway and its role in the pathogenesis of BCCs, smoothened (SMO) inhibitors have been developed with Sonidegib being the 2nd in class. It is the only Hh pathway inhibitor investigated in a randomized trial accompanied by pharmacodynamic investigations...
October 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27534889/neglected-skin-cancer-in-the-elderly-a-case-of-basosquamous-cell-carcinoma-of-the-right-shoulder
#20
Erika Bisgaard, Michael Tarakji, Frank Lau, Adam Riker
Skin cancer remains the most common cancer worldwide, and basal cell carcinoma represents the largest portion of non-melanomatous skin cancers with over 3 million cases diagnosed annually. Locally advanced disease is frequently seen in the elderly posing clinical challenges regarding proper treatment.We report on an 86-year-old female presenting with fatigue, anemia and a large ulcerated skin lesion along the right upper back. A biopsy of the lesion revealed a basosquamous cell carcinoma. She underwent a wide local excision with complex wound reconstruction...
2016: Journal of Surgical Case Reports
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