Literature DB >> 28286127

Hedgehog Signaling: From Basic Biology to Cancer Therapy.

Fujia Wu1, Yu Zhang2, Bo Sun2, Andrew P McMahon3, Yu Wang4.   

Abstract

The Hedgehog (HH) signaling pathway was discovered originally as a key pathway in embryonic patterning and development. Since its discovery, it has become increasingly clear that the HH pathway also plays important roles in a multitude of cancers. Therefore, HH signaling has emerged as a therapeutic target of interest for cancer therapy. In this review, we provide a brief overview of HH signaling and the key molecular players involved and offer an up-to-date summary of our current knowledge of endogenous and exogenous small molecules that modulate HH signaling. We discuss experiences and lessons learned from the decades-long efforts toward the development of cancer therapies targeting the HH pathway. Challenges to develop next-generation cancer therapies are highlighted.
Copyright © 2017 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  GLI; basal cell carcinoma; cancer therapy; cholesterol; drug resistance; endogenous smoothened regulation; hedgehog signaling; medulloblastoma; smoothened; stem cell

Mesh:

Substances:

Year:  2017        PMID: 28286127      PMCID: PMC7442121          DOI: 10.1016/j.chembiol.2017.02.010

Source DB:  PubMed          Journal:  Cell Chem Biol        ISSN: 2451-9448            Impact factor:   8.116


  224 in total

1.  Arsenic antagonizes the Hedgehog pathway by preventing ciliary accumulation and reducing stability of the Gli2 transcriptional effector.

Authors:  Jynho Kim; John J Lee; James Kim; Dale Gardner; Philip A Beachy
Journal:  Proc Natl Acad Sci U S A       Date:  2010-07-12       Impact factor: 11.205

2.  Smoothened variants explain the majority of drug resistance in basal cell carcinoma.

Authors:  Scott X Atwood; Kavita Y Sarin; Ramon J Whitson; Jiang R Li; Geurim Kim; Melika Rezaee; Mina S Ally; Jinah Kim; Catherine Yao; Anne Lynn S Chang; Anthony E Oro; Jean Y Tang
Journal:  Cancer Cell       Date:  2015-03-09       Impact factor: 31.743

3.  A Phase I Study of FOLFIRINOX Plus IPI-926, a Hedgehog Pathway Inhibitor, for Advanced Pancreatic Adenocarcinoma.

Authors:  Andrew H Ko; Noelle LoConte; Margaret A Tempero; Evan J Walker; R Kate Kelley; Stephanie Lewis; Wei-Chou Chang; Emily Kantoff; Michael W Vannier; Daniel V Catenacci; Alan P Venook; Hedy L Kindler
Journal:  Pancreas       Date:  2016-03       Impact factor: 3.327

4.  Teratogen-mediated inhibition of target tissue response to Shh signaling.

Authors:  M K Cooper; J A Porter; K E Young; P A Beachy
Journal:  Science       Date:  1998-06-05       Impact factor: 47.728

5.  A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia.

Authors:  Karolin V Dorn; Casey E Hughes; Rajat Rohatgi
Journal:  Dev Cell       Date:  2012-09-13       Impact factor: 12.270

6.  Phase I study of the Hedgehog pathway inhibitor IPI-926 in adult patients with solid tumors.

Authors:  Antonio Jimeno; Glen J Weiss; Wilson H Miller; Scott Gettinger; Bernard J C Eigl; Anne Lynne S Chang; Joi Dunbar; Shannon Devens; Kerrie Faia; Georgios Skliris; Jeff Kutok; Karl D Lewis; Raoul Tibes; William H Sharfman; Robert W Ross; Charles M Rudin
Journal:  Clin Cancer Res       Date:  2013-04-10       Impact factor: 12.531

7.  Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma.

Authors:  Robert L Yauch; Gerrit J P Dijkgraaf; Bruno Alicke; Thomas Januario; Christina P Ahn; Thomas Holcomb; Kanan Pujara; Jeremy Stinson; Christopher A Callahan; Tracy Tang; J Fernando Bazan; Zhengyan Kan; Somasekar Seshagiri; Christine L Hann; Stephen E Gould; Jennifer A Low; Charles M Rudin; Frederic J de Sauvage
Journal:  Science       Date:  2009-09-02       Impact factor: 47.728

8.  Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine.

Authors:  J Taipale; J K Chen; M K Cooper; B Wang; R K Mann; L Milenkovic; M P Scott; P A Beachy
Journal:  Nature       Date:  2000-08-31       Impact factor: 49.962

9.  Reduced cholesterol levels impair Smoothened activation in Smith-Lemli-Opitz syndrome.

Authors:  Robert Blassberg; James I Macrae; James Briscoe; John Jacob
Journal:  Hum Mol Genet       Date:  2015-12-18       Impact factor: 6.150

10.  Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar-ductal metaplasia.

Authors:  Xin Liu; Jason R Pitarresi; Maria C Cuitiño; Raleigh D Kladney; Sarah A Woelke; Gina M Sizemore; Sunayana G Nayak; Onur Egriboz; Patrick G Schweickert; Lianbo Yu; Stefan Trela; Daniel J Schilling; Shannon K Halloran; Maokun Li; Shourik Dutta; Soledad A Fernandez; Thomas J Rosol; Gregory B Lesinski; Reena Shakya; Thomas Ludwig; Stephen F Konieczny; Gustavo Leone; Jinghai Wu; Michael C Ostrowski
Journal:  Genes Dev       Date:  2016-09-15       Impact factor: 11.361

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  93 in total

1.  Computer-Aided Discovery and Characterization of Novel Ebola Virus Inhibitors.

Authors:  Stephen J Capuzzi; Wei Sun; Eugene N Muratov; Carles Martínez-Romero; Shihua He; Wenjun Zhu; Hao Li; Gregory Tawa; Ethan G Fisher; Miao Xu; Paul Shinn; Xiangguo Qiu; Adolfo García-Sastre; Wei Zheng; Alexander Tropsha
Journal:  J Med Chem       Date:  2018-04-17       Impact factor: 7.446

Review 2.  Mixed signals from the cell's antennae: primary cilia in cancer.

Authors:  Thibaut Eguether; Michael Hahne
Journal:  EMBO Rep       Date:  2018-10-22       Impact factor: 8.807

Review 3.  Lineage-specific roles of hedgehog-GLI signaling during mammalian kidney development.

Authors:  Robert D'Cruz; Katryna Stronks; Christopher J Rowan; Norman D Rosenblum
Journal:  Pediatr Nephrol       Date:  2019-03-28       Impact factor: 3.714

4.  Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms.

Authors:  Michael Skaro; Neha Nanda; Christian Gauthier; Matthäus Felsenstein; Zhengdong Jiang; Miaozhen Qiu; Koji Shindo; Jun Yu; Danielle Hutchings; Ammar A Javed; Ross Beckman; Jin He; Christopher L Wolfgang; Elizabeth Thompson; Ralph H Hruban; Alison P Klein; Michael Goggins; Laura D Wood; Nicholas J Roberts
Journal:  Gastroenterology       Date:  2019-02-01       Impact factor: 22.682

Review 5.  TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Serotonin and the regulation of calcium transport in dairy cows.

Authors:  L L Hernandez
Journal:  J Anim Sci       Date:  2017-12       Impact factor: 3.159

6.  Sonic Hedgehog as a Regulator of Endometrial Mesenchymal Stem/Stromal Cell Activity.

Authors:  James A Deane
Journal:  Mol Ther       Date:  2020-01-17       Impact factor: 11.454

7.  Rapid, direct activity assays for Smoothened reveal Hedgehog pathway regulation by membrane cholesterol and extracellular sodium.

Authors:  Benjamin R Myers; Lila Neahring; Yunxiao Zhang; Kelsey J Roberts; Philip A Beachy
Journal:  Proc Natl Acad Sci U S A       Date:  2017-12-11       Impact factor: 11.205

Review 8.  Structure, regulation, and (patho-)physiological functions of the stress-induced protein kinase CK1 delta (CSNK1D).

Authors:  Pengfei Xu; Chiara Ianes; Fabian Gärtner; Congxing Liu; Timo Burster; Vasiliy Bakulev; Najma Rachidi; Uwe Knippschild; Joachim Bischof
Journal:  Gene       Date:  2019-07-31       Impact factor: 3.688

9.  Loss of Primary Cilia Drives Switching from Hedgehog to Ras/MAPK Pathway in Resistant Basal Cell Carcinoma.

Authors:  François Kuonen; Noelle E Huskey; Gautam Shankar; Prajakta Jaju; Ramon J Whitson; Kerri E Rieger; Scott X Atwood; Kavita Y Sarin; Anthony E Oro
Journal:  J Invest Dermatol       Date:  2019-01-29       Impact factor: 8.551

10.  Smoothening out the patches.

Authors:  Anselm Sommer; Mark A Lemmon
Journal:  Science       Date:  2018-10-05       Impact factor: 47.728

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