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Vismodegib

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https://www.readbyqxmd.com/read/28546761/spotlight-on-vismodegib-in-the-treatment-of-basal-cell-carcinoma-an-evidence-based-review-of-its-place-in-therapy
#1
REVIEW
Zoe Apalla, Chrysoula Papageorgiou, Aimilios Lallas, Elena Sotiriou, Elizabeth Lazaridou, Efstratios Vakirlis, Athanassios Kyrgidis, Demetrios Ioannides
Vismodegib is approved for the treatment of adult patients with metastatic (mBCC) or locally advanced basal cell carcinoma (laBCC) that have recurred following surgery or for those who are not good candidates for surgery (risk/benefit ratio is against patient's benefit, either because of the general condition or because of the expected morbidity from the surgery) or radiation therapy. This article provides an evidence-based review of its current place in therapy. Analytically, the clinical implications in the management of laBCCs and mBCCs and possible new indications, including the neoadjuvant use before surgical excision, are discussed, while in the end, the challenges regarding class-related adverse events and their optimal management are highlighted...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28525403/genetic-diseases-associated-with-an-increased-risk-of-skin-cancer-development-in-childhood
#2
Alexander L Fogel, Kavita Y Sarin, Joyce M C Teng
PURPOSE OF REVIEW: Childhood skin cancers are relatively rare and may indicate an underlying genetic disorder. The increasing elucidation of genetic pathways is changing the diagnosis and management of genetic skin cancer susceptibility syndromes. In this review, we provide an overview of genetic conditions that predispose to skin cancer development in childhood and signs that providers should assess when evaluating affected individuals. RECENT FINDINGS: In basal cell nevus syndrome (BCNS), the patched2 (PTCH2) and suppressor of fused (SUFU) genes have been implicated in disease pathogenesis...
May 18, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28523596/pharmacokinetics-and-safety-of-vismodegib-in-patients-with-advanced-solid-malignancies-and-hepatic-impairment
#3
Ghassan K Abou-Alfa, Lionel D Lewis, Patricia LoRusso, Michael Maitland, Priya Chandra, Sravanthi Cheeti, Dawn Colburn, Sarah Williams, Brian Simmons, Richard A Graham
PURPOSE: Vismodegib is a Hedgehog pathway inhibitor approved for the treatment of advanced basal cell carcinoma. Currently, the pharmacokinetics (PK) and safety of vismodegib in patients with hepatic dysfunction are unknown and are the objective of this study. METHODS: Patients with advanced solid malignancies and hepatic impairment were enrolled into one of four cohorts: normal [bilirubin (bili) < upper limit of normal (ULN)], mild (ULN < bili ≤ 1...
May 18, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28511673/long-term-safety-and-efficacy-of-vismodegib-in-patients-with-advanced-basal-cell-carcinoma-final-update-of-the-pivotal-erivance-bcc-study
#4
Aleksandar Sekulic, Michael R Migden, Nicole Basset-Seguin, Claus Garbe, Anja Gesierich, Christopher D Lao, Chris Miller, Laurent Mortier, Dedee F Murrell, Omid Hamid, Jorge F Quevedo, Jeannie Hou, Edward McKenna, Natalie Dimier, Sarah Williams, Dirk Schadendorf, Axel Hauschild
BACKGROUND: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC...
May 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28507440/ocular-basal-cell-carcinoma-a-brief-literature-review-of-clinical-diagnosis-and-treatment
#5
REVIEW
Yingyun Shi, Renbing Jia, Xianqun Fan
Basal cell carcinoma (BCC) is a common malignant tumor throughout the world. One of the known risk factors of BCC is intense exposure to ultraviolet radiation. More than 50% of BCCs of the eyelid initially occur on the lower lid. The gold standard of diagnosis of BCC is histopathology. Treatment options for BCC consist of surgery, vismodegib, radiotherapy and imiquimod. Surgical excision using Mohs micrographic surgery or wide surgical excision with frozen section margin control is the first consideration for treatment of periocular BCC...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28458774/triple-hedgehog-pathway-inhibition-for-basal-cell-carcinoma
#6
Xinyi Yang, Matthew S Dinehart
Vismodegib, a potent inhibitor of the hedgehog pathway, is an effective treatment for advanced basal cell carcinoma. More recently, it has become recognized that other oral and topical medications exist that also inhibit this pathway. Multifocal inhibition has been shown to work more efficaciously than a single pathway inhibition when treating melanocytic tumors. The authors report the successful treatment of a patient with advanced basal cell carcinoma using the combination of vismodegib, itraconazole, and imiquimod, each of which inhibits a different part of the hedgehog pathway...
April 2017: Journal of Clinical and Aesthetic Dermatology
https://www.readbyqxmd.com/read/28408356/possible-antifibrotic-effect-of-gdc-0449-vismodegib-a-hedgehog-pathway-inhibitor-in-mice-model-of-schistosoma-induced-liver-fibrosis
#7
Abeer A Elhenawy, Rehab H Ashour, Nairmen Nabih, Naglaa M Shalaby, Nirmeen Megahed
Liver fibrosis is a pathological process complicating schistosomiasis. It is an active process of continuous extracellular matrix accumulation. In Egypt, schistosomiasis re-infection is a continuing problem especially in rural areas. In this study we examined the antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor as a new molecular target for Schistosoma-induced liver fibrosis, in addition to exploring its effect as antischistosomal drug. The effect of GDC-0449 alone or combined with Praziquantel was tried experimentally in infected mice with Schistosoma mansoni...
April 10, 2017: Parasitology International
https://www.readbyqxmd.com/read/28404762/implementation-of-systemic-hedgehog-inhibitors-in-daily-practice-as-neoadjuvant-therapy
#8
REVIEW
Nikki Tang, Desiree Ratner
The most common cancer in both men and women is basal cell carcinoma (BCC). Although most primary and recurrent BCCs have high cure rates with standard therapies, advanced BCCs present a greater treatment challenge, especially in cosmetically and functionally sensitive areas. In patients unable to undergo surgery or radiation therapy, hedgehog inhibitors can be used neoadjuvantly to reduce tumor size, decreasing the extent and complexity of any subsequent surgery and providing either a cure or palliation. The goal of this review is to summarize the pharmacology, efficacy, and safety of systemic hedgehog inhibitors, as well as their role in daily practice as neoadjuvant therapy...
April 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28398426/reversible-cutaneous-side-effects-of-vismodegib-treatment
#9
Bernice Kwong, Christina Danial, Andy Liu, Kimberly A Chun, Anne Lynn S Chang
No abstract text is available yet for this article.
March 2017: Cutis; Cutaneous Medicine for the Practitioner
https://www.readbyqxmd.com/read/28352196/sonidegib-mechanism-of-action-pharmacology-and-clinical-utility-for-advanced-basal-cell-carcinomas
#10
REVIEW
Sachin Jain, Ruolan Song, Jingwu Xie
The Hedgehog (Hh) pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC), medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA) approved sonidegib, a smoothened (SMO) antagonist, for treatment of advanced BCC (aBCC) after a successful Phase II clinical trial...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28302010/discovery-of-hedgehog-antagonists-for-cancer-therapy
#11
Harleen Khatra, Chandra Bose, Surajit Sinha
BACKGROUND: The evolutionarily conserved Hedgehog (Hh) signaling cascade is one of the key mediators of embryonic development of many metazoans. This pathway has been extensively targeted by small molecule inhibitors as its misregulation leads to various malignancies and developmental disorders. Thus, blocking this pathway can be a novel therapeutic avenue for the treatment of Hedgehog-dependent cancers. This review covers the mechanism of hedgehog signaling in vertebrate cells, provides an overview of reported small molecule Hh pathway inhibitors, with the synthetic routes and SAR studies of some of them discussed briefly...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28297142/vismodegib-therapy-for-basal-cell-carcinoma-in-an-8-year-old-chinese-boy-with-xeroderma-pigmentosum
#12
Douglas Fife, Marko A Laitinen, David J Myers, Pamela B Landsteiner
Vismodegib is an oral inhibitor of the Hedgehog signaling pathway and has been used to treat basal cell carcinoma (BCC) in adults. This article reports clearance of a nodular BCC of the nasal tip in an 8-year-old boy with xeroderma pigmentosum (XP). BCC can pose therapeutic challenges when located in areas that are not amenable to traditional therapies such as Mohs micrographic surgery or topical agents. Vismodegib was used at a dose of 150 mg/day to treat the boy's BCC. After 4 months of therapy, we achieved complete clinical clearance...
March 2017: Pediatric Dermatology
https://www.readbyqxmd.com/read/28276480/selective-targeting-of-hdac1-2-elicits-anticancer-effects-through-gli1-acetylation-in-preclinical-models-of-shh-medulloblastoma
#13
Sonia Coni, Anna Barbara Mancuso, Laura Di Magno, Giulia Sdruscia, Simona Manni, Silvia Maria Serrao, Dante Rotili, Eleonora Spiombi, Francesca Bufalieri, Marialaura Petroni, Monika Kusio-Kobialka, Enrico De Smaele, Elisabetta Ferretti, Carlo Capalbo, Antonello Mai, Pawel Niewiadomski, Isabella Screpanti, Lucia Di Marcotullio, Gianluca Canettieri
SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28250200/cxcl14-is-a-candidate-biomarker-for-hedgehog-signalling-in-idiopathic-pulmonary-fibrosis
#14
Guiquan Jia, Sanjay Chandriani, Alexander R Abbas, Daryle J DePianto, Elsa N N'Diaye, Murat B Yaylaoglu, Heather M Moore, Ivan Peng, Jason DeVoss, Harold R Collard, Paul J Wolters, Jackson G Egen, Joseph R Arron
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity. METHODS: We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor...
March 1, 2017: Thorax
https://www.readbyqxmd.com/read/28202523/cancer-stem-cells-regulate-cancer-associated-fibroblasts-via-activation-of-hedgehog-signaling-in-mammary-gland-tumors
#15
Giovanni Valenti, Hazel M Quinn, Guus J J E Heynen, Linxiang Lan, Jane D Holland, Regina Vogel, Annika Wulf-Goldenberg, Walter Birchmeier
Many tumors display intracellular heterogeneity with subsets of cancer stem cells (CSC) that sustain tumor growth, recurrence, and therapy resistance. Cancer-associated fibroblasts (CAF) have been shown to support and regulate CSC function. Here, we investigate the interactions between CSCs and CAFs in mammary gland tumors driven by combined activation of Wnt/β-catenin and Hgf/Met signaling in mouse mammary epithelial cells. In this setting, CSCs secrete the Hedgehog ligand SHH, which regulate CAFs via paracrine activation of Hedgehog signaling...
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28196186/statistical-concerns-on-vismodegib-for-basal-cell-carcinoma-meta-analysis
#16
Joao Paulo da Silveira Nogueira Lima
No abstract text is available yet for this article.
April 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28196183/statistical-concerns-on-vismodegib-for-basal-cell-carcinoma-meta-analysis-reply
#17
Audrey A Jacobsen, John Strasswimmer
No abstract text is available yet for this article.
April 1, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28194541/undermining-plastic-surgery-as-a%C3%A2-possible-option-for-treating-basal-cell-carcinoma-of-the-forehead
#18
Georgi Tchernev, Ivan Pidakev, Ilia Lozev, Torello Lotti, Jose Carlos Cardoso, James W Patterson
Basal cell carcinoma (BCC) is the most common cutaneous cancer. Although most cases can be cured with simple surgical procedures and are associated with a good prognosis, a minority of BCCs may pose significant therapeutic challenges. This occurs mostly in cases of so-called advanced BCC, which a loosely defined term that encompasses locally advanced lesions and tumors with metastatic spread. Treatment of these cases is often complex and sometimes may need combinations of therapeutic modalities, including surgery, radiotherapy and/or targeted therapy directed towards sonic hedgehog (SHH) signaling pathways, such as vismodegib...
April 2017: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28188087/intermittent-vismodegib-dosing-to-treat-multiple-basal-cell-carcinomas
#19
Klara Mosterd
No abstract text is available yet for this article.
March 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28188086/two-intermittent-vismodegib-dosing-regimens-in-patients-with-multiple-basal-cell-carcinomas-mikie-a-randomised-regimen-controlled-double-blind-phase-2-trial
#20
Brigitte Dréno, Rainer Kunstfeld, Axel Hauschild, Scott Fosko, David Zloty, Bruno Labeille, Jean-Jacques Grob, Susana Puig, Frank Gilberg, Daniel Bergström, Damian R Page, Gary Rogers, Dirk Schadendorf
BACKGROUND: Vismodegib, a first-in-class Hedgehog-pathway inhibitor, is approved for use in adults with advanced basal-cell carcinoma. Patients with multiple basal-cell carcinomas, including those with basal-cell nevus (Gorlin) syndrome, need extended treatment. We assessed the safety and activity of two long-term intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas. METHODS: In this randomised, regimen-controlled, double-blind, phase 2 trial, we enrolled adult patients with multiple basal-cell carcinomas, including those with basal-cell nevus syndrome, who had one or more histopathologically confirmed and at least six clinically evident basal-cell carcinomas...
March 2017: Lancet Oncology
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