Recent Advances in the Clinical Targeting of Hedgehog/GLI Signaling in Cancer

Phase Ib Study of Glasdegib, a Hedgehog Pathway Inhibitor, in Combination with Standard Chemotherapy in Patients with AML or High-Risk MDS

(2018) Michael R. Savona et al.   CLINICAL CANCER RESEARCH

GANT-61 and GDC-0449 induce apoptosis of prostate cancer stem cells through a GLI-dependent mechanism

(2018) Wangxia Tong et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial

(2017) N. Basset-Séguin et al.   EUROPEAN JOURNAL OF CANCER

Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial

(2017) Brigitte Dréno et al.   LANCET ONCOLOGY

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

(2017) Mark W Kieran et al.   NEURO-ONCOLOGY

Anti-cell growth and anti-cancer stem cell activities of the non-canonical hedgehog inhibitor GANT61 in triple-negative breast cancer cells

(2017) Yoshikazu Koike et al.   Breast Cancer

445ODOSE-ESCALATION STUDY OF SONIDEGIB (LDE225) PLUS BUPARLISIB (BKM120) IN PATIENTS (PTS) WITH ADVANCED SOLID TUMORS

(2017) Q.S. Chu et al.   ANNALS OF ONCOLOGY

A randomized phase II study of vismodegib (V), a hedgehog (HH) pathway inhibitor, combined with FOLFOX in patients (pts) with advanced gastric and gastroesophageal junction (GEJ) carcinoma: A New York Cancer Consortium led study.

(2017) Deirdre Jill Cohen et al.   JOURNAL OF CLINICAL ONCOLOGY

Inhibition of Hedgehog signaling for the treatment of lymphoma and CLL: a phase II study from the LYSA: Table 1.

(2016) R. Houot et al.   ANNALS OF ONCOLOGY

Vismodegib or cixutumumab in combination with standard chemotherapy for patients with extensive-stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E1508)

(2016) Chandra P. Belani et al.   CANCER

Pharmacodynamic study of the oral hedgehog pathway inhibitor, vismodegib, in patients with metastatic castration-resistant prostate cancer

(2016) Benjamin L. Maughan et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Phase I, multicenter, open-label, dose-escalation study of sonidegib in Asian patients with advanced solid tumors

(2016) Hironobu Minami et al.   CANCER SCIENCE

Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells

(2016) Nobuaki Fukushima et al.   CANCER SCIENCE

GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment

(2016) Jianlong Li et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

Inhibition of the hedgehog pathway in patients with basal-cell nevus syndrome: final results from the multicentre, randomised, double-blind, placebo-controlled, phase 2 trial

(2016) Jean Y Tang et al.   LANCET ONCOLOGY

A phase I trial of the Hedgehog inhibitor, sonidegib (LDE225), in combination with etoposide and cisplatin for the initial treatment of extensive stage small cell lung cancer

(2016) M. Catherine Pietanza et al.   LUNG CANCER

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

(2016) Andrew H. Ko et al.   PANCREAS

Smoothened Variants Explain the Majority of Drug Resistance in Basal Cell Carcinoma

(2015) Scott X. Atwood et al.   CANCER CELL

Genomic Analysis of Smoothened Inhibitor Resistance in Basal Cell Carcinoma

(2015) Hayley J. Sharpe et al.   CANCER CELL

An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib

(2015) C. Danial et al.   CLINICAL CANCER RESEARCH

Randomized Phase Ib/II Study of Gemcitabine Plus Placebo or Vismodegib, a Hedgehog Pathway Inhibitor, in Patients With Metastatic Pancreatic Cancer

(2015) Daniel V.T. Catenacci et al.   JOURNAL OF CLINICAL ONCOLOGY

Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog–Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032

(2015) Giles W. Robinson et al.   JOURNAL OF CLINICAL ONCOLOGY

A phase II, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma

(2015) Howard Sofen et al.   JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial

(2015) Michael R Migden et al.   LANCET ONCOLOGY

Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial

(2015) Nicole Basset-Seguin et al.   LANCET ONCOLOGY

Phase II evaluation of IPI-926, an oral Hedgehog inhibitor, in patients with myelofibrosis

(2015) Koji Sasaki et al.   LEUKEMIA & LYMPHOMA

An In Vivo Chemical Genetic Screen Identifies Phosphodiesterase 4 as a Pharmacological Target for Hedgehog Signaling Inhibition

(2015) Charles H. Williams et al.   Cell Reports

Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study

(2015) Giovanni Martinelli et al.   Lancet Haematology

A Phase I Study of PF-04449913, an Oral Hedgehog Inhibitor, in Patients with Advanced Solid Tumors

(2014) A. J. Wagner et al.   CLINICAL CANCER RESEARCH

Phase I Dose-Escalation Trial of the Oral Investigational Hedgehog Signaling Pathway Inhibitor TAK-441 in Patients with Advanced Solid Tumors

(2014) J. Goldman et al.   CLINICAL CANCER RESEARCH

A Phase I, Multicenter, Open-Label, First-in-Human, Dose-Escalation Study of the Oral Smoothened Inhibitor Sonidegib (LDE225) in Patients with Advanced Solid Tumors

(2014) J. Rodon et al.   CLINICAL CANCER RESEARCH

Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC-0449 (Vismodegib) in Combination with Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

(2014) E. J. Kim et al.   CLINICAL CANCER RESEARCH

Open-Label, Exploratory Phase II Trial of Oral Itraconazole for the Treatment of Basal Cell Carcinoma

(2014) Daniel J. Kim et al.   JOURNAL OF CLINICAL ONCOLOGY

An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma

(2014) Mina Sarah Ally et al.   JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

The sonic hedgehog factor GLI1 imparts drug resistance through inducible glucuronidation

(2014) Hiba Ahmad Zahreddine et al.   NATURE

Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition

(2014) Yujie Tang et al.   NATURE MEDICINE

GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma Group/US and French National Cancer Institute Single-Arm Phase II Collaborative Study

(2013) A. Italiano et al.   ANNALS OF ONCOLOGY

Itraconazole and Arsenic Trioxide Inhibit Hedgehog Pathway Activation and Tumor Growth Associated with Acquired Resistance to Smoothened Antagonists

(2013) James Kim et al.   CANCER CELL

Phase I Study of the Hedgehog Pathway Inhibitor IPI-926 in Adult Patients with Solid Tumors

(2013) A. Jimeno et al.   CLINICAL CANCER RESEARCH

Phase I Study of Vismodegib in Children with Recurrent or Refractory Medulloblastoma: A Pediatric Brain Tumor Consortium Study

(2013) A. Gajjar et al.   CLINICAL CANCER RESEARCH

Emergence of a squamous cell carcinoma phenotype following treatment of metastatic basal cell carcinoma with vismodegib

(2013) Amy Iarrobino et al.   JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY

Phase 2 Study of Pemetrexed and Itraconazole as Second-Line Therapy for Metastatic Nonsquamous Non–Small-Cell Lung Cancer

(2013) Charles M. Rudin et al.   Journal of Thoracic Oncology

GLI activation by atypical protein kinase C ι/λ regulates the growth of basal cell carcinomas

(2013) Scott X. Atwood et al.   NATURE

Repurposing Itraconazole as a Treatment for Advanced Prostate Cancer: A Noncomparative Randomized Phase II Trial in Men With Metastatic Castration-Resistant Prostate Cancer

(2013) E. S. Antonarakis et al.   ONCOLOGIST

Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: Modification of the core skeleton for improved solubility

(2012) Tomohiro Ohashi et al.   BIOORGANIC & MEDICINAL CHEMISTRY

GANT-61 inhibits pancreatic cancer stem cell growth in vitro and in NOD/SCID/IL2R gamma null mice xenograft

(2012) Junsheng Fu et al.   CANCER LETTERS

A Phase II, Randomized, Placebo-Controlled Study of Vismodegib as Maintenance Therapy in Patients with Ovarian Cancer in Second or Third Complete Remission

(2012) S. B. Kaye et al.   CLINICAL CANCER RESEARCH

A Randomized Phase II Trial of Vismodegib versus Placebo with FOLFOX or FOLFIRI and Bevacizumab in Patients with Previously Untreated Metastatic Colorectal Cancer

(2012) J. Berlin et al.   CLINICAL CANCER RESEARCH

CLIN-ONGOING CLINICAL TRIALS

(2012) M. Furuse et al.   NEURO-ONCOLOGY

Inhibiting the Hedgehog Pathway in Patients with the Basal-Cell Nevus Syndrome

(2012) Jean Y. Tang et al.   NEW ENGLAND JOURNAL OF MEDICINE

Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma

(2012) Aleksandar Sekulic et al.   NEW ENGLAND JOURNAL OF MEDICINE

Phase I Trial of Hedgehog Pathway Inhibitor Vismodegib (GDC-0449) in Patients with Refractory, Locally Advanced or Metastatic Solid Tumors

(2011) P. M. LoRusso et al.   CLINICAL CANCER RESEARCH

Inhibition of Hedgehog Signaling Antagonizes Serous Ovarian Cancer Growth in a Primary Xenograft Model

(2011) Christopher K. McCann et al.   PLoS One

Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened

(2011) Michael J. Munchhof et al.   ACS Medicinal Chemistry Letters

Hedgehog beyond medulloblastoma and basal cell carcinoma

(2010) Stephan Teglund et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

Assessing the efficacy of the Hedgehog pathway inhibitor vitamin D3 in a murine xenograft model for pancreatic cancer

(2010) Lois W. Brüggemann et al.   CANCER BIOLOGY & THERAPY

Itraconazole, a Commonly Used Antifungal that Inhibits Hedgehog Pathway Activity and Cancer Growth

(2010) James Kim et al.   CANCER CELL

Overexpression of Smoothened Activates the Sonic Hedgehog Signaling Pathway in Pancreatic Cancer-Associated Fibroblasts

(2010) K. Walter et al.   CLINICAL CANCER RESEARCH

Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway

(2010) Elspeth M. Beauchamp et al.   JOURNAL OF CLINICAL INVESTIGATION

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

(2010) J. Kim et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Interfering with Resistance to Smoothened Antagonists by Inhibition of the PI3K Pathway in Medulloblastoma

(2010) S. Buonamici et al.   Science Translational Medicine

Desmoplasia of Pancreatic Ductal Adenocarcinoma

(2009) Stephen Pandol et al.   Clinical Gastroenterology and Hepatology

Discovery of a Potent and Orally Active Hedgehog Pathway Antagonist (IPI-926)

(2009) Martin R. Tremblay et al.   JOURNAL OF MEDICINAL CHEMISTRY

Inhibition of the Hedgehog Pathway in Advanced Basal-Cell Carcinoma

(2009) Daniel D. Von Hoff et al.   NEW ENGLAND JOURNAL OF MEDICINE

Smoothened Mutation Confers Resistance to a Hedgehog Pathway Inhibitor in Medulloblastoma

(2009) R. L. Yauch et al.   SCIENCE

Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer

(2009) K. P. Olive et al.   SCIENCE

Sonic Hedgehog Promotes Desmoplasia in Pancreatic Cancer

(2008) J. M. Bailey et al.   CLINICAL CANCER RESEARCH

An orally bioavailable small-molecule inhibitor of Hedgehog signaling inhibits tumor initiation and metastasis in pancreatic cancer

(2008) G. Feldmann et al.   MOLECULAR CANCER THERAPEUTICS

A paracrine requirement for hedgehog signalling in cancer

(2008) Robert L. Yauch et al.   NATURE