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Sonidegib

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https://www.readbyqxmd.com/read/29551110/odomzo-%C3%A2-sonidegib
#1
Aditya K Gupta, Rachel R Mays, William Abramovits, Kimberly Dawn Vincent
No abstract text is available yet for this article.
2018: Skinmed
https://www.readbyqxmd.com/read/29515801/recurrent-extraneural-sonic-hedgehog-medulloblastoma-exhibiting-sustained-response-to-vismodegib-and-temozolomide-monotherapies-and-inter-metastatic-molecular-heterogeneity-at-progression
#2
Gregorio J Petrirena, Julien Masliah-Planchon, Quentin Sala, Bertrand Pourroy, Didier Frappaz, Emeline Tabouret, Thomas Graillon, Jean-Claude Gentet, Olivier Delattre, Olivier Chinot, Laetitia Padovani
Background: Response to targeting and non-targeting agents is variable and molecular information remains poorly described in patients with recurrent sonic-hedgehog-driven medulloblastoma (SHH-MB). Materials and Methods: Clinical and PET/CT findings during treatment with successive hedgehog antagonists and temozolomide monotherapies are described in a heavily pre-treated patient with recurrent extraneural metastases from PTCH1 mutated/ wild type smoothened ( SMO ) CNS SHH-MB...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29484007/locally-advanced-basal-cell-carcinoma-with-intraocular-invasion
#3
Georgi Tchernev, Torello Lotti, Ilia Lozev, Georgi Konstantinov Maximov, Uwe Wollina
We present a 103 - year - old patient, with duration of complaints of about ten years. The initial complaint had been presented as a small nodule, located on the eyebrow, which subsequently ulcerated and encompassed larger regions of the upper and lower eyelids. For the past three years, the patient also had complaints of a worsening of his vision, without seeking for medical help. Within the dermatological examination, an intraocular and periocular localised tumour was established, characterised by a raised peripheral edge and central ulceration...
January 25, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29454489/basal-cell-nevus-syndrome-gorlin-syndrome-genetic-insights-diagnostic-challenges-and-unmet-milestones
#4
Maryam Akbari, Harold Chen, Grace Guo, Zachary Legan, Ghali Ghali
In this article, we present three clinical case reports on Basal Cell Nevus Syndrome (Gorlin Syndrome). Gorlin syndrome is an inherited medical condition with challenges that manifest in multiple body systems and complicate early diagnosis. We examine the epidemiology of the disease and benefits of genetic testing, molecular pathophysiology, and advancement in the molecular-based therapy of Basal Cell Nevus syndrome. The goal of this paper is to shed light on both unmet challenges and advancements in the management of Gorlin syndrome and to provide a new clinical perspective and guidance for future research...
January 31, 2018: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/29407368/emerging-trends-in-the-treatment-of-advanced-basal-cell-carcinoma
#5
REVIEW
Michael R Migden, Anne Lynn S Chang, Luc Dirix, Alexander J Stratigos, John T Lear
Basal cell carcinoma (BCC) is the most commonly diagnosed skin cancer worldwide. In most patients, BCC can be effectively treated with standard surgical excision, Mohs micrographic surgery, curettage and electrodessication, radiotherapy, and/or superficial field therapies (including 5-fluorouracil, imiquimod, and photodynamic therapy); however, a minority of patients develop advanced BCC, for which treatment can be challenging and outcomes are poorer. Advanced BCC encompasses a heterogeneous assortment of cases, including metastatic BCC as well as locally advanced BCC (for which no formal definition exists but which generally includes large, deep, aggressive, or recurrent tumors)...
March 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29387745/intracranial-regression-of-an-advanced-basal-cell-carcinoma-using-sonidegib-and-itraconazole-after-failure-with-vismodegib
#6
Jaeyoung Yoon, Anthony J Apicelli, Tricia V Pavlopoulos
No abstract text is available yet for this article.
January 2018: JAAD Case Reports
https://www.readbyqxmd.com/read/29326074/overcoming-the-resistance-mechanisms-of-smoothened-inhibitors
#7
REVIEW
Xiaochun Dong, Chenglin Wang, Zhongjian Chen, Weili Zhao
Smoothened (Smo), the main transducer of the Hedgehog (Hh) signaling pathway, is a promising target for anticancer therapy. Although vismodegib and sonidegib have demonstrated effectiveness for the treatment of basal cell carcinoma (BCC), their clinical use has been associated with mutation-related drug resistance. In this review, we outline the resistance mechanisms of Smo inhibitors and point the way for future endeavors. We focus in particular on the development of second-generation Smo inhibitors based on co-crystal structures, inhibition of downstream components, and the regulation of other interacting pathways or mediators that could compensate for the inhibitory activity of upstream inhibitors...
March 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29315702/strategies-to-target-the-hedgehog-signaling-pathway-for-cancer-therapy
#8
REVIEW
Minhang Xin, Xinyue Ji, Ladie Kimberly De La Cruz, Suresh Thareja, Binghe Wang
Hedgehog (Hh) signaling is an essential pathway in the human body, and plays a major role in embryo development and tissue patterning. Constitutive activation of the Hh signaling pathway through sporadic mutations or other mechanisms is explicitly associated with cancer development and progression in various solid malignancies. Therefore, targeted inhibition of the Hh signaling pathway has emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Vismodegib, a first-in-class Hh signaling pathway inhibitor was approved by the US Food and Drug Administration in 2012, and sonidegib, another potent Hh pathway inhibitor, received FDA's approval in 2015 as a new treatment of locally advanced or metastatic basal cell carcinoma...
January 5, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29296838/phase-1-study-of-the-hedgehog-pathway-inhibitor-sonidegib-for-steroid-refractory-chronic-graft-versus-host-disease
#9
Zachariah DeFilipp, Rosalynn M Nazarian, Areej El-Jawahri, Shuli Li, Jami Brown, Candice Del Rio, Melissa Smith, Betsy Valles, Karen K Ballen, Steven L McAfee, Jacalyn Rosenblatt, Joseph H Antin, Corey S Cutler, Yi-Bin Chen
Hedgehog signaling plays a key role in tissue fibrosis, the pathological hallmark of chronic graft-versus-host disease (cGVHD). We conducted a phase 1 trial of sonidegib, a selective antagonist of the hedgehog coreceptor Smoothened, for the treatment of steroid-refractory cGVHD. After a 3+3 study design, sonidegib was administered for up to 12 cycles of 28 days each, using 3 doses: 200 mg/day (dose level 1), 400 mg/day (dose level 2), and 600 mg/day (dose level 3). Seventeen patients were enrolled. The median number of cycles completed was 6 (range, 0-12)...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29274272/the-role-of-the-hedgehog-signaling-pathway-in-cancer-a-comprehensive-review
#10
REVIEW
Ana Marija Skoda, Dora Simovic, Valentina Karin, Vedran Kardum, Semir Vranic, Ljiljana Serman
The Hedgehog (Hh) signaling pathway was first identified in the common fruit fly. It is a highly conserved evolutionary pathway of signal transmission from the cell membrane to the nucleus. The Hh signaling pathway plays an important role in the embryonic development. It exerts its biological effects through a signaling cascade that culminates in a change of balance between activator and repressor forms of glioma-associated oncogene (Gli) transcription factors. The components of the Hh signaling pathway involved in the signaling transfer to the Gli transcription factors include Hedgehog ligands (Sonic Hh [SHh], Indian Hh [IHh], and Desert Hh [DHh]), Patched receptor (Ptch1, Ptch2), Smoothened receptor (Smo), Suppressor of fused homolog (Sufu), kinesin protein Kif7, protein kinase A (PKA), and cyclic adenosine monophosphate (cAMP)...
February 20, 2018: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29208776/losers-of-primary-cilia-gain-the-benefit-of-survival
#11
COMMENT
Gladiola Goranci-Buzhala, Elke Gabriel, Aruljothi Mariappan, Jay Gopalakrishnan
<b/> In this issue, Zhao and colleagues demonstrate that loss of primary cilia in medulloblastoma cells confers resistance to the Smoothened (SMO) inhibitor sonidegib. When treated with sonidegib, medulloblastoma cells lost their cilia and gained resistance. Surprisingly, loss of cilia is associated with recurrent mutations in ciliogenesis genes that are eventually able to drive drug resistance. These findings uncover a previously unknown mechanism of cancer cells in gaining a "persister-like" state against anticancer agents at the expense of losing primary cilia...
December 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29197167/to-take-or-not-to-take-with-meals-unraveling-issues-related-to-food-effects-labeling-for-oral-antineoplastic-drugs
#12
Jiexin Deng, Satjit S Brar, Lawrence J Lesko
There has been controversy regarding whether bioavailability of certain oral oncology drugs should be maximized by taking these medications with food, irrespective of label instructions in the dosing and administration section. To provide insight into this controversy, we conducted an in-depth analysis for oral antineoplastic drugs approved by the Food and Drug Administration in 2000-2016 and identified important issues influencing food labeling decisions. Furthermore, a case study involving sonidegib, a drug approved for locally advanced basal cell carcinoma with a significant food effect on exposure, was used to demonstrate the consequences of failure to adhere to food label recommendations using drug-specific population pharmacokinetic and exposure-toxicity models...
December 2, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29175429/an-exploratory-open-label-investigator-initiated-study-to-evaluate-the-efficacy-and-safety-of-combination-sonidegib-and-buparlisib-for-advanced-basal-cell-carcinomas
#13
Duy Cong Tran, Ann Moffat, Richard Brotherton, Alana Pague, Gefei Alex Zhu, Anne Lynn S Chang
No abstract text is available yet for this article.
November 23, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29133390/recovery-of-taste-organs-and-sensory-function-after-severe-loss-from-hedgehog-smoothened-inhibition-with-cancer-drug-sonidegib
#14
Archana Kumari, Alexandre N Ermilov, Marina Grachtchouk, Andrzej A Dlugosz, Benjamin L Allen, Robert M Bradley, Charlotte M Mistretta
Striking taste disturbances are reported in cancer patients treated with Hedgehog (HH)-pathway inhibitor drugs, including sonidegib (LDE225), which block the HH pathway effector Smoothened (SMO). We tested the potential for molecular, cellular, and functional recovery in mice from the severe disruption of taste-organ biology and taste sensation that follows HH/SMO signaling inhibition. Sonidegib treatment led to rapid loss of taste buds (TB) in both fungiform and circumvallate papillae, including disruption of TB progenitor-cell proliferation and differentiation...
November 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29131041/skin-manifestations-of-targeted-antineoplastic-therapy
#15
Onofre Sanmartín
The management of oncology patients has changed significantly over recent years, with the development of new targeted anticancer therapies. Cutaneous adverse effects are among the most frequently observed toxicities with many targeted agents; their intensity can be dose-limiting or lead to the discontinuation of therapy. Tyrosine kinase inhibitors can cause maculopapular rash and hand-foot reaction, whereas papulopustular rash, paronychia, regulatory changes in hair, and dryness are caused by epidermal growth factor receptor inhibitors...
2018: Current Problems in Dermatology
https://www.readbyqxmd.com/read/29119833/treatment-of-advanced-basal-cell-carcinoma-with-sonidegib-perspective-from-the-30-month-update-of-the-bolt-trial
#16
Leon Chen, Alexander B Aria, Sirunya Silapunt, Heng-Huan Lee, Michael R Migden
Sonidegib, a hedgehog pathway inhibitor, was approved by the US FDA for the treatment of locally advanced basal cell carcinoma which cannot be readily treated with surgery or radiotherapy. The pharmacology and pharmacokinetics of sonidegib will be discussed in this review. Additionally, an in-depth analysis of the BOLT trial and data from the 30-month update will be included. This will serve as an update to a previously published article which reported the 12-month update of the BOLT trial.
March 2018: Future Oncology
https://www.readbyqxmd.com/read/28887802/small-molecule-inhibitors-of-the-hedgehog-pathway-in-the-treatment-of-basal-cell-carcinoma-of-the-skin
#17
REVIEW
Rebecca Danhof, Karl Lewis, Mariah Brown
Basal cell carcinoma (BCC) is the most common type of skin cancer, with rising incidence rates primarily attributed to an aging population and ultraviolet radiation exposure. While the majority of BCCs are localized and respond to standard therapies, a very small minority of these tumors become locally destructive or metastasize. These advanced BCCs may not be amenable to localized treatment with surgery and/or radiation therapy. Most BCCs result from mutations in key receptors in the Hedgehog (HH) signaling pathway...
September 8, 2017: American Journal of Clinical Dermatology
https://www.readbyqxmd.com/read/28846163/long-term-efficacy-and-safety-of-sonidegib-in-patients-with-locally-advanced-and-metastatic-basal-cell-carcinoma-30-month-analysis-of-the-randomized-phase-2-bolt-study
#18
J T Lear, M R Migden, K D Lewis, A L S Chang, A Guminski, R Gutzmer, L Dirix, P Combemale, A Stratigos, R Plummer, H Castro, T Yi, M Mone, J Zhou, U Trefzer, M Kaatz, C Loquai, R Kudchadkar, D Sellami, R Dummer
BACKGROUND: Patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), 2 difficult-to-treat populations, have had limited treatment options. Sonidegib, a hedgehog pathway inhibitor (HPI), was approved in laBCC based on results from the BOLT trial. OBJECTIVE: To evaluate long-term efficacy and safety of sonidegib in laBCC and mBCC in the BOLT 18- and 30-month analyses. METHODS: BOLT (NCT01327053, ClinicalTrials. gov), a double-blind phase 2 study, enrolled patients from July 2011 until January 2013...
August 28, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28789624/hedgehog-inhibitor-sonidegib-potentiates-177-lu-octreotate-therapy-of-got1-human-small-intestine-neuroendocrine-tumors-in-nude-mice
#19
Johan Spetz, Britta Langen, Nils Rudqvist, Toshima Z Parris, Khalil Helou, Ola Nilsson, Eva Forssell-Aronsson
BACKGROUND: (177)Lu-octreotate can be used to treat somatostatin receptor expressing neuroendocrine tumors. It is highly effective in animal models, but clinical studies have so far only demonstrated low cure rates. Hedgehog inhibitors have shown therapeutic effect as monotherapy in neuroendocrine tumor model systems and might be one option to enhance the efficacy of (177)Lu-octreotate therapy. The aim of this study was to determine the therapeutic effect of combination therapy using (177)Lu-octreotate and the Hedgehog signaling pathway inhibitor sonidegib...
August 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28738360/targeting-developmental-pathways-the-achilles-heel-of-cancer
#20
REVIEW
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Timothy Chevassut
Developmental pathways (e.g., Notch, Hippo, Hedgehog, Wnt, and TGF-β/BMP/FGF) are networks of genes that act co-ordinately to establish the body plan, and disruptions of genes in one pathway can have effects in related pathways and may result in serious dysmorphogenesis or cancer. Interestingly, all developmental pathways are highly conserved cell signalling systems present in almost all multicellular organisms. In addition, they have a crucial role in cell proliferation, apoptosis, differentiation, and finally in organ development...
2017: Oncology
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