Repurposing Vandetanib plus Everolimus for the Treatment of ACVR1-Mutant Diffuse Intrinsic Pontine Glioma

Combined vandetanib and everolimus was identified by artificial intelligence as a potential therapy for ACVR1-mutant DIPG, as they synergize in vitro and extend survival in vivo, with preliminary testing in four children suggesting this combination as a feasible clinical option.

[1]  K. Hess,et al.  Safety and activity of vandetanib in combination with everolimus in patients with advanced solid tumors: a phase I study , 2021, ESMO open.

[2]  Cameron R. Wolfe,et al.  Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19 , 2020, The New England journal of medicine.

[3]  Saee Paliwal,et al.  Preclinical validation of therapeutic targets predicted by tensor factorization on heterogeneous graphs , 2020, Scientific Reports.

[4]  F. Baldanti,et al.  Mechanism of baricitinib supports artificial intelligence‐predicted testing in COVID‐19 patients , 2020, EMBO molecular medicine.

[5]  T. Aittokallio,et al.  SynergyFinder 2.0: visual analytics of multi-drug combination synergies , 2020, Nucleic Acids Res..

[6]  M. Corbellino,et al.  Baricitinib for COVID-19: a suitable treatment? – Authors' reply , 2020, The Lancet Infectious Diseases.

[7]  R. Caporali,et al.  Baricitinib for COVID-19: a suitable treatment? , 2020, The Lancet Infectious Diseases.

[8]  Ivan Griffin,et al.  COVID-19: combining antiviral and anti-inflammatory treatments , 2020, The Lancet Infectious Diseases.

[9]  A. Phelan,et al.  Baricitinib as potential treatment for 2019-nCoV acute respiratory disease , 2020, The Lancet.

[10]  A. Chinnaiyan,et al.  Everolimus improves the efficacy of dasatinib in PDGFRα-driven glioma. , 2020, The Journal of clinical investigation.

[11]  Damien Y. Duveau,et al.  Therapeutic strategies for diffuse midline glioma from high-throughput combination drug screening , 2019, Science Translational Medicine.

[12]  Albert A Antolin,et al.  Transforming cancer drug discovery with Big Data and AI , 2019, Expert opinion on drug discovery.

[13]  M. Monje,et al.  ALK2 inhibitors display beneficial effects in preclinical models of ACVR1 mutant diffuse intrinsic pontine glioma , 2019, Communications Biology.

[14]  R. McLendon,et al.  ACVR1 R206H cooperates with H3.1K27M in promoting diffuse intrinsic pontine glioma pathogenesis , 2019, Nature Communications.

[15]  N. Pavlakis,et al.  Anti-angiogenic therapy for high-grade glioma. , 2018, The Cochrane database of systematic reviews.

[16]  T. Isobe,et al.  A Low Crizotinib Concentration in the Cerebrospinal Fluid Causes Ineffective Treatment of Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer with Carcinomatous Meningitis , 2018, Internal medicine.

[17]  P. Robertson,et al.  CSF H3F3A K27M circulating tumor DNA copy number quantifies tumor growth and in vitro treatment response , 2018, Acta Neuropathologica Communications.

[18]  M. Monje,et al.  Drug screening linked to molecular profiling identifies novel dependencies in patient-derived primary cultures of paediatric high grade glioma and DIPG , 2018, bioRxiv.

[19]  Chris Jones,et al.  DIPG-29. PRECLINICAL EFFICACY OF COMBINED ACVR1 AND PI3K/mTOR INHIBITION IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) , 2018, Neuro-Oncology.

[20]  K. Hess,et al.  Multi-kinase RET inhibitor vandetanib combined with mTOR inhibitor everolimus in patients with RET rearranged non-small cell lung cancer. , 2018 .

[21]  S. Khatua,et al.  Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  Kun Mu,et al.  Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma , 2017, Cancer cell.

[23]  David T. W. Jones,et al.  Development of the SIOPE DIPG network, registry and imaging repository: a collaborative effort to optimize research into a rare and lethal disease , 2017, Journal of Neuro-Oncology.

[24]  Adam Lane,et al.  The international diffuse intrinsic pontine glioma registry: an infrastructure to accelerate collaborative research for an orphan disease , 2017, Journal of Neuro-Oncology.

[25]  David T. W. Jones,et al.  Pediatric high-grade glioma: biologically and clinically in need of new thinking , 2016, Neuro-oncology.

[26]  M. Monje,et al.  Contemporary survival endpoints: an International Diffuse Intrinsic Pontine Glioma Registry study. , 2016, Neuro-oncology.

[27]  David T. W. Jones,et al.  Pseudoprogression in children, adolescents and young adults with non-brainstem high grade glioma and diffuse intrinsic pontine glioma , 2016, Journal of Neuro-Oncology.

[28]  S. Quake,et al.  Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases , 2016, Journal of Neuro-Oncology.

[29]  Lily Huang,et al.  ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A , 2015, Science Translational Medicine.

[30]  V. Miller,et al.  Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged non-small cell lung cancer with brain metastases. , 2015, Lung cancer.

[31]  S. Puget,et al.  Preclinical evaluation of dasatinib alone and in combination with cabozantinib for the treatment of diffuse intrinsic pontine glioma. , 2015, Neuro-oncology.

[32]  Nicholas J. Wang,et al.  Functionally-defined Therapeutic Targets in Diffuse Intrinsic Pontine Glioma , 2015, Nature Medicine.

[33]  Noah E. Berlow,et al.  A High-Throughput In Vitro Drug Screen in a Genetically Engineered Mouse Model of Diffuse Intrinsic Pontine Glioma Identifies BMS-754807 as a Promising Therapeutic Agent , 2015, PloS one.

[34]  Chris Jones,et al.  ACVR1 mutations in DIPG: lessons learned from FOP. , 2014, Cancer research.

[35]  A. Bullock,et al.  Structure–Activity Relationship of 3,5-Diaryl-2-aminopyridine ALK2 Inhibitors Reveals Unaltered Binding Affinity for Fibrodysplasia Ossificans Progressiva Causing Mutants , 2014, Journal of medicinal chemistry.

[36]  R. Herbst,et al.  EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer , 2014, Annals of oncology : official journal of the European Society for Medical Oncology.

[37]  Stephen Yip,et al.  Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma , 2014, Nature Genetics.

[38]  Liliana Goumnerova,et al.  Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma , 2014, Nature Genetics.

[39]  Amar Gajjar,et al.  The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma , 2014, Nature Genetics.

[40]  Michael Brudno,et al.  Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations , 2014, Nature Genetics.

[41]  S-M Huang,et al.  Why Clinical Modulation of Efflux Transport at the Human Blood–Brain Barrier Is Unlikely: The ITC Evidence‐Based Position , 2013, Clinical pharmacology and therapeutics.

[42]  Edward S. Kim,et al.  Clinical and Biomarker Outcomes of the Phase II Vandetanib Study from the BATTLE Trial , 2013, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[43]  J. Villano,et al.  Bevacizumab and central nervous system (CNS) hemorrhage , 2013, Cancer Chemotherapy and Pharmacology.

[44]  Amar Gajjar,et al.  Phase I Trial, Pharmacokinetics, and Pharmacodynamics of Vandetanib and Dasatinib in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma , 2013, Clinical Cancer Research.

[45]  B. Qin,et al.  Co-administration strategy to enhance brain accumulation of vandetanib by modulating P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (Bcrp1/Abcg2) mediated efflux with m-TOR inhibitors. , 2012, International journal of pharmaceutics.

[46]  Darren Hargrave,et al.  Paediatric and adult malignant glioma: close relatives or distant cousins? , 2012, Nature Reviews Clinical Oncology.

[47]  John V Heymach,et al.  Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome. , 2012, Journal of the National Cancer Institute.

[48]  David T. W. Jones,et al.  Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma , 2012, Nature.

[49]  Li Ding,et al.  Somatic Histone H3 Alterations in Paediatric Diffuse Intrinsic Pontine Gliomas and Non-Brainstem Glioblastomas , 2012, Nature Genetics.

[50]  Amar Gajjar,et al.  Phase I study of vandetanib during and after radiotherapy in children with diffuse intrinsic pontine glioma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[51]  Sabine Tejpar,et al.  Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. , 2010, The Lancet. Oncology.

[52]  A. Marchetti,et al.  Clinical implications of KRAS mutations in lung cancer patients treated with tyrosine kinase inhibitors: an important role for mutations in minor clones. , 2009, Neoplasia.

[53]  Suzanne F. Jones,et al.  Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[54]  P. Houghton,et al.  Phase I study of everolimus in pediatric patients with refractory solid tumors. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[55]  B. Groner,et al.  Mammalian target of rapamycin regulates the growth of mammary epithelial cells through the inhibitor of deoxyribonucleic acid binding Id1 and their functional differentiation through Id2. , 2006, Molecular endocrinology.

[56]  L. Wodicka,et al.  A small molecule–kinase interaction map for clinical kinase inhibitors , 2005, Nature Biotechnology.

[57]  Pfister,et al.  DECIPHER pooled shRNA library screen identifies PP2A and FGFR signaling as potential therapeutic targets for diffuse intrinsic pontine gliomas , 2019 .

[58]  P. Varlet,et al.  Radiotherapy with concurrent and adjuvant temozolomide in children with newly diagnosed diffuse intrinsic pontine glioma , 2011, Journal of Neuro-Oncology.

[59]  Massimo Zucchetti,et al.  Tyrosine kinase inhibitors and multidrug resistance proteins: interactions and biological consequences , 2009, Cancer Chemotherapy and Pharmacology.

[60]  R A Patchell,et al.  Brain metastases. , 1991, Neurologic clinics.