keyword
MENU ▼
Read by QxMD icon Read
search

Sonidegib

keyword
https://www.readbyqxmd.com/read/29208776/losers-of-primary-cilia-gain-the-benefit-of-survival
#1
Gladiola Goranci-Buzhala, Elke Gabriel, Aruljothi Mariappan, Jay Gopalakrishnan
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
#2
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
#3
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
#4
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 13, 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
#5
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
#6
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.
November 9, 2017: 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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28626889/from-basal-cell-carcinoma-morphogenesis-to-the-alopecia-induced-by-hedgehog-inhibitors-connecting-the-dots
#11
REVIEW
C Dessinioti, C Antoniou, A J Stratigos
The deciphering of the hedgehog (Hh) signalling pathway implicated in the tumorigenesis of basal cell carcinoma (BCC) led to the development of targeted drug therapies, the Hh pathway inhibitors (HPIs) vismodegib and sonidegib. In the skin, physiological Hh signalling is activated in growing hair follicles (HFs), where it is required for proliferation of the epithelium of HFs during morphogenesis and for their postnatal growth. The effects of HPI treatment leading to the regression of BCC and the development of alopecia underpin the central role of the Hh pathway in BCC formation, as well as hair cycling...
June 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28607774/a-matching-adjusted-indirect-comparison-of-sonidegib-and-vismodegib-in-advanced-basal-cell-carcinoma
#12
Dawn Odom, Deirdre Mladsi, Molly Purser, James A Kaye, Eirini Palaka, Alina Charter, Jo Annah Jensen, Dalila Sellami
OBJECTIVES: Based on single-arm trial data (BOLT), sonidegib was approved in the US and EU to treat locally advanced basal cell carcinomas (BCCs) ineligible for curative surgery or radiotherapy. Vismodegib, the other approved targeted therapy, also was assessed in a single-arm trial (ERIVANCE). We examined the comparative effectiveness of the two drugs using a matching-adjusted indirect comparison (MAIC) versus an unadjusted indirect comparison. METHODS: After comparing trials and identifying potential prognostic factors, an MAIC was conducted to adjust for differences in key patient baseline characteristics...
2017: Journal of Skin Cancer
https://www.readbyqxmd.com/read/28605510/phase-i-study-of-oral-sonidegib-lde225-in-pediatric-brain-and-solid-tumors-and-a-phase-ii-study-in-children-and-adults-with-relapsed-medulloblastoma
#13
Mark W Kieran, Julia Chisholm, Michela Casanova, Alba A Brandes, Isabelle Aerts, Eric Bouffet, Simon Bailey, Sarah Leary, Tobey J MacDonald, Francoise Mechinaud, Kenneth J Cohen, Riccardo Riccardi, Warren Mason, Darren Hargrave, Stacey Kalambakas, Priya Deshpande, Feng Tai, Eunju Hurh, Birgit Geoerger
Background: Sonidegib (LDE225) is a potent, selective hedgehog (Hh) inhibitor of Smoothened. This study explored the safety and pharmacokinetics of sonidegib in children with relapsed/recurrent tumors followed by a phase II trial in pediatric and adult patients with relapsed medulloblastoma (MB) to assess tumor response. Methods: Pediatric patients aged ≥1 to <18 years were included according to a Bayesian design starting at 372 mg/m2 of continuous once daily oral sonidegib...
October 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28577129/effects-of-mild-to-severe-hepatic-impairment-on-the-pharmacokinetics-of-sonidegib-a-multicenter-open-label-parallel-group-study
#14
Yves Horsmans, Jocelyn Zhou, Mateva Liudmila, George Golor, Oren Shibolet, Michelle Quinlan, Corinne Emotte, Hildegard Boss, Henry Castro, Dalila Sellami, Richard A Preston
BACKGROUND AND OBJECTIVE: Sonidegib is a potent, selective and orally bioavailable inhibitor of the Hedgehog signaling pathway, primarily metabolized by the liver. In order to make dose recommendations for patients with hepatic impairment, we have assessed here the pharmacokinetics (PKs) and safety of sonidegib in subjects with varying degrees of hepatic function. METHODS: The primary objective of this phase I, multicenter, open-label study was to evaluate the PKs of a single oral 800 mg dose of sonidegib in subjects with impaired hepatic function compared with healthy subjects...
June 2, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28560483/conditional-loss-of-hepatocellular-hedgehog-signaling-in-female-mice-leads-to-the-persistence-of-hepatic-steroidogenesis-androgenization-and-infertility
#15
Christiane Rennert, Franziska Eplinius, Ute Hofmann, Janina Johänning, Franziska Rolfs, Wolfgang Schmidt-Heck, Reinhardt Guthke, Rolf Gebhardt, Albert M Ricken, Madlen Matz-Soja
The Hedgehog signaling pathway is known to be involved in embryogenesis, tissue remodeling, and carcinogenesis. Because of its involvement in carcinogenesis, it seems an interesting target for cancer therapy. Indeed, Sonidegib, an approved inhibitor of the Hedgehog receptor Smoothened (Smo), is highly active against diverse carcinomas, but its use is also reported to be associated with several systemic side effects. Our former work in adult mice demonstrated hepatic Hedgehog signaling to play a key role in the insulin-like growth factor axis and lipid metabolism...
May 30, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28416737/efficacy-of-continuous-egfr-inhibition-and-role-of-hedgehog-in-egfr-acquired-resistance-in-human-lung-cancer-cells-with-activating-mutation-of-egfr
#16
Carminia Maria Della Corte, Umberto Malapelle, Elena Vigliar, Francesco Pepe, Giancarlo Troncone, Vincenza Ciaramella, Teresa Troiani, Erika Martinelli, Valentina Belli, Fortunato Ciardiello, Floriana Morgillo
PURPOSE: The aim of this work was to investigate the efficacy of sequential treatment with first-, second- and third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and the mechanisms of acquired resistance occurring during the sequential use of these inhibitors. EXPERIMENTAL DESIGN: We developed an in vivo model of acquired resistance to EGFR-inhibitors by treating nude mice xenografted with HCC827, a human non-small-cell lung cancer (NSCLC) cell line harboring EGFR activating mutation, with a sequence of first-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs) (erlotinib and gefitinib), of second-generation EGFR-TKI (afatinib) plus/minus the anti-EGFR monoclonal antibody cetuximab, and of third-generation EGFR-TKI (osimertinib)...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404762/implementation-of-systemic-hedgehog-inhibitors-in-daily-practice-as-neoadjuvant-therapy
#17
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/28352196/sonidegib-mechanism-of-action-pharmacology-and-clinical-utility-for-advanced-basal-cell-carcinomas
#18
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/28317088/phase-i-trial-of-the-oral-smoothened-inhibitor-sonidegib-in-combination-with-paclitaxel-in-patients-with-advanced-solid-tumors
#19
A Stathis, D Hess, R von Moos, K Homicsko, G Griguolo, M Joerger, M Mark, C J Ackermann, S Allegrini, C V Catapano, A Xyrafas, M Enoiu, S Berardi, P Gargiulo, C Sessa
Purpose To establish a recommended phase II dose (RP2D) for the oral smoothened inhibitor sonidegib in combination with paclitaxel; secondary objectives include evaluation of safety, tolerability, markers of Hedgehog (Hh) signaling and preliminary antitumor activity. Methods Patients with advanced solid tumors were enrolled in cohorts of escalating sonidegib dose levels (400mg, 600mg and 800mg orally, once daily on days 1-28) in combination with paclitaxel 80 mg/m(2) on days 1, 8 and 15 in 4-weekly cycles. Dose-limiting toxicities (DLTs) were assessed using CTCAE v4...
December 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28182134/differential-pharmacology-and-clinical-utility-of-sonidegib-in-advanced-basal-cell-carcinoma
#20
REVIEW
Mohd Wahid, Arshad Jawed, Sajad Ahmad Dar, Raju K Mandal, Shafiul Haque
Patients suffering from advanced basal cell carcinoma (BCC) have very limited treatment options. Sonidegib selectively inhibits the growth of Hedgehog pathway-dependent tumors and can treat locally advanced BCC patients who are not candidates for surgery or radiation therapy. The BOLT clinical trials were conducted to evaluate the efficacy/potency of sonidegib in the treatment of advanced BCC or metastatic BCC. The patients were randomized in 1:2 ratios to receive 200 or 800 mg oral sonidegib daily, stratified by disease, histological subtype and geographical region...
2017: OncoTargets and Therapy
keyword
keyword
64518
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"