PI3K/mTOR Pathway Inhibition: Opportunities in Oncology and Rare Genetic Diseases

Overgrowth syndromes — clinical and molecular aspects and tumour risk

(2019) Frédéric Brioude et al.   Nature Reviews Endocrinology

New insights into a spectrum of developmental malformations related to mTOR dysregulations: challenges and perspectives

(2019) A. Mühlebner et al.   JOURNAL OF ANATOMY

PDK1 Mediates NOTCH1-Mutated Head and Neck Squamous Carcinoma Vulnerability to Therapeutic PI3K/mTOR Inhibition

(2019) Vaishnavi Sambandam et al.   CLINICAL CANCER RESEARCH

The “other” mTOR complex: New insights into mTORC 2 immunobiology and their implications

(2019) Helong Dai et al.   AMERICAN JOURNAL OF TRANSPLANTATION

First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma

(2019) Chiara Leoni et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART A

Targeting PI3K signaling in cancer: Challenges and advances

(2019) Maria Chiara De Santis et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review

(2019) Mahnaz Jamee et al.   CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY

Duvelisib: a new phosphoinositide-3-kinase inhibitor in chronic lymphocytic leukemia

(2019) Anna M Frustaci et al.   Future Oncology

Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer

(2019) Fabrice André et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting the PI3K/Akt/mTOR pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases

(2019) Franziska Maria Ippen et al.   NEURO-ONCOLOGY

The PTEN–PI3K Axis in Cancer

(2019) Papa et al.   Biomolecules

MicroRNA‑21‑5p targeting PDCD4 suppresses apoptosis via regulating the PI3K/AKT/FOXO1 signaling pathway in tongue squamous cell carcinoma

(2019) Changfu Liu et al.   Experimental and Therapeutic Medicine

Comparative Effects of Topical 0.2% Sirolimus for Angiofibromas in Adults and Pediatric Patients with Tuberous Sclerosis Complex

(2018) Young In Lee et al.   DERMATOLOGY

65 YEARS OF THE DOUBLE HELIX: One gene, many endocrine and metabolic syndromes: PTEN -opathies and precision medicine

(2018) Lamis Yehia et al.   ENDOCRINE-RELATED CANCER

Everolimus dosing recommendations for tuberous sclerosis complex-associated refractory seizures

(2018) David N. Franz et al.   EPILEPSIA

Strategies for Enhancing the Permeation of CNS-Active Drugs through the Blood-Brain Barrier: A Review

(2018) Isra’ Zeiadeh et al.   MOLECULES

Review: Mechanistic target of rapamycin (mTOR) pathway, focal cortical dysplasia and epilepsy

(2018) E. Marsan et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Efficacy and Safety of Topical Rapamycin in Patients With Facial Angiofibromas Secondary to Tuberous Sclerosis Complex

(2018) Mary Kay Koenig et al.   JAMA Dermatology

Activated PI3 Kinase Delta Syndrome: From Genetics to Therapy

(2018) David Michalovich et al.   Frontiers in Immunology

Down-regulation of Rictor enhances cell sensitivity to PI3K inhibitor LY294002 by blocking mTORC2-medicated phosphorylation of Akt/PRAS40 in esophageal squamous cell carcinoma

(2018) Guiqin Hou et al.   BIOMEDICINE & PHARMACOTHERAPY

Targeted therapy in patients with PIK3CA-related overgrowth syndrome

(2018) Quitterie Venot et al.   NATURE

The novel, catalytic mTORC1/2 inhibitor PQR620 and the PI3K/mTORC1/2 inhibitor PQR530 effectively cross the blood-brain barrier and increase seizure threshold in a mouse model of chronic epilepsy

(2018) Claudia Brandt et al.   NEUROPHARMACOLOGY

Effect of Buparlisib, a Pan-Class I PI3K Inhibitor, in Refractory Follicular and Poorly Differentiated Thyroid Cancer

(2018) Francoise Borson-Chazot et al.   THYROID

Cancer-Associated PIK3CA Mutations in Overgrowth Disorders

(2018) Ralitsa R. Madsen et al.   TRENDS IN MOLECULAR MEDICINE

Discovery and Preclinical Characterization of 5-[4,6-Bis({3-oxa-8-azabicyclo[3.2.1]octan-8-yl})-1,3,5-triazin-2-yl]-4-(difluoromethyl)pyridin-2-amine (PQR620), a Highly Potent and Selective mTORC1/2 Inhibitor for Cancer and Neurological Disorders

(2018) Denise Rageot et al.   JOURNAL OF MEDICINAL CHEMISTRY

Phase Ib dose-finding study of abiraterone acetate plus buparlisib (BKM120) or dactolisib (BEZ235) in patients with castration-resistant prostate cancer

(2017) Christophe Massard et al.   EUROPEAN JOURNAL OF CANCER

Phase II trial of the PI3 kinase inhibitor buparlisib (BKM-120) with or without enzalutamide in men with metastatic castration resistant prostate cancer

(2017) Andrew J. Armstrong et al.   EUROPEAN JOURNAL OF CANCER

Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing

(2017) Paul Kuentz et al.   GENETICS IN MEDICINE

Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma

(2017) Anas Younes et al.   HAEMATOLOGICA

MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells

(2017) Russell G. Jones et al.   IMMUNITY

Targeting the Mammalian Target of Rapamycin for Epileptic Encephalopathies and Malformations of Cortical Development

(2017) Anna Jeong et al.   JOURNAL OF CHILD NEUROLOGY

5-(4,6-Dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine (PQR309), a Potent, Brain-Penetrant, Orally Bioavailable, Pan-Class I PI3K/mTOR Inhibitor as Clinical Candidate in Oncology

(2017) Florent Beaufils et al.   JOURNAL OF MEDICINAL CHEMISTRY

Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development

(2017) Hua-fu Zhao et al.   Molecular Cancer

Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

(2017) Richard S. Finkel et al.   NEW ENGLAND JOURNAL OF MEDICINE

Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors

(2017) Klemens Hoegenauer et al.   ACS Medicinal Chemistry Letters

Deconvolution of Buparlisib’s mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention

(2017) Thomas Bohnacker et al.   Nature Communications

CC-115, a dual inhibitor of mTOR Kinase and DNA-PK, blocks DNA damage repair pathways and selectively inhibits ATM-deficient cell growth in vitro

(2017) Toshiya Tsuji et al.   Oncotarget

Pan-phosphatidylinositol 3-kinase inhibition with buparlisib in patients with relapsed or refractory non-Hodgkin lymphoma

(2017) Anas Younes et al.   HAEMATOLOGICA

PI3K Signaling in Tissue Hyper-Proliferation: From Overgrowth Syndromes to Kidney Cysts

(2017) Maria De Santis et al.   Cancers

TAK-228 (formerly MLN0128), an investigational oral dual TORC1/2 inhibitor: A phase I dose escalation study in patients with relapsed or refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenström's macroglobulinemia

(2016) Irene M. Ghobrial et al.   AMERICAN JOURNAL OF HEMATOLOGY

Nephroblastomatosis or Wilms tumor in a fourth patient with a somaticPIK3CAmutation

(2016) Karen W. Gripp et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART A

Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies

(2016) Kim M. Keppler-Noreuil et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS

Brain somatic mutations in MTOR leading to focal cortical dysplasia

(2016) Jae Seok Lim et al.   BMB Reports

Dactolisib (NVP-BEZ235) toxicity in murine brain tumour models

(2016) I. A. Netland et al.   BMC CANCER

A Randomised Phase 2 Study of AZD2014 Versus Everolimus in Patients with VEGF-Refractory Metastatic Clear Cell Renal Cancer

(2016) Thomas Powles et al.   EUROPEAN UROLOGY

Everolimus in patients with advanced follicular-derived thyroid cancer; results of a phase II clinical trial.

(2016) T.C. Schneider et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study

(2016) Jacqueline A French et al.   LANCET

Intermittent High-Dose Scheduling of AZD8835, a Novel Selective Inhibitor of PI3K  and PI3K , Demonstrates Treatment Strategies for PIK3CA-Dependent Breast Cancers

(2016) K. Hudson et al.   MOLECULAR CANCER THERAPEUTICS

Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement

(2016) Lawrence S. Hsieh et al.   Nature Communications

Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis, and Immunotherapy

(2016) K. Okkenhaug et al.   Cancer Discovery

Association ofMTORMutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism

(2016) Ghayda M. Mirzaa et al.   JAMA Neurology

Tuberous sclerosis complex

(2016) Elizabeth P. Henske et al.   Nature Reviews Disease Primers

Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulatorNPRL3

(2015) Joe C. Sim et al.   ANNALS OF NEUROLOGY

A phase I dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mTORC1/mTORC2 kinase inhibitor CC-223 in patients with advanced solid tumors or multiple myeloma

(2015) Johanna C. Bendell et al.   CANCER

Pre-clinical evaluation of AZD-2014, a novel mTORC1/2 dual inhibitor, against renal cell carcinoma

(2015) Bing Zheng et al.   CANCER LETTERS

First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014

(2015) B. Basu et al.   CLINICAL CANCER RESEARCH

AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules

(2015) S. M. Guichard et al.   MOLECULAR CANCER THERAPEUTICS

Survival benefit and phenotypic improvement by hamartin gene therapy in a tuberous sclerosis mouse brain model

(2015) Shilpa Prabhakar et al.   NEUROBIOLOGY OF DISEASE

Clinical delineation and natural history of thePIK3CA-related overgrowth spectrum

(2014) Kim M. Keppler-Noreuil et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART A

Focal dysplasia of the cerebral cortex and infantile spasms associated with somatic 1q21.1-q44 duplication including theAKT3gene

(2014) V. Conti et al.   CLINICAL GENETICS

An mTOR anti-sense oligonucleotide decreases polycystic kidney disease in mice with a targeted mutation in Pkd2

(2014) Kameswaran Ravichandran et al.   HUMAN MOLECULAR GENETICS

Characterization of the Activity of the PI3K/mTOR Inhibitor XL765 (SAR245409) in Tumor Models with Diverse Genetic Alterations Affecting the PI3K Pathway

(2014) P. Yu et al.   MOLECULAR CANCER THERAPEUTICS

PI3K and cancer: lessons, challenges and opportunities

(2014) David A. Fruman et al.   NATURE REVIEWS DRUG DISCOVERY

PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma

(2014) Ajay K. Gopal et al.   NEW ENGLAND JOURNAL OF MEDICINE

A Diverse Array of Cancer-Associated MTOR Mutations Are Hyperactivating and Can Predict Rapamycin Sensitivity

(2014) B. C. Grabiner et al.   Cancer Discovery

Everolimus treatment of refractory epilepsy in tuberous sclerosis complex

(2013) Darcy A. Krueger et al.   ANNALS OF NEUROLOGY

BAY 80-6946 Is a Highly Selective Intravenous PI3K Inhibitor with Potent p110α and p110δ Activities in Tumor Cell Lines and Xenograft Models

(2013) Ningshu Liu et al.   MOLECULAR CANCER THERAPEUTICS

Mammalian Target of Rapamycin (mTOR) Pathways in Neurological Diseases

(2013) Michael Wong   Biomedical Journal

mTOR Signaling in Growth Control and Disease

(2012) Mathieu Laplante et al.   CELL

Phosphoinositide 3-Kinase (PI3K) Pathway Alterations Are Associated with Histologic Subtypes and Are Predictive of Sensitivity to PI3K Inhibitors in Lung Cancer Preclinical Models

(2012) J. M. Spoerke et al.   CLINICAL CANCER RESEARCH

Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA

(2012) Marjorie J Lindhurst et al.   NATURE GENETICS

Targeted therapy in rare cancers—adopting the orphans

(2012) Javier Munoz et al.   Nature Reviews Clinical Oncology

Somatic Activation of AKT3 Causes Hemispheric Developmental Brain Malformations

(2012) Annapurna Poduri et al.   NEURON

Modulators of Sensitivity and Resistance to Inhibition of PI3K Identified in a Pharmacogenomic Screen of the NCI-60 Human Tumor Cell Line Collection

(2012) Kevin A. Kwei et al.   PLoS One

Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis

(2011) Nicole A. Neuman et al.   EMBO Molecular Medicine

Rapamycin passes the torch: a new generation of mTOR inhibitors

(2011) Don Benjamin et al.   NATURE REVIEWS DRUG DISCOVERY

Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1)

(2010) Laura R. Pearce et al.   BIOCHEMICAL JOURNAL

Predictive Biomarkers of Sensitivity to the Phosphatidylinositol 3' Kinase Inhibitor GDC-0941 in Breast Cancer Preclinical Models

(2010) C. O'Brien et al.   CLINICAL CANCER RESEARCH

Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis

(2010) Darcy A. Krueger et al.   NEW ENGLAND JOURNAL OF MEDICINE

Intranasally delivered siRNA targeting PI3K/Akt/mTOR inflammatory pathways protects from aspergillosis

(2009) P Bonifazi et al.   Mucosal Immunology

Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex

(2008) Ling-Hui Zeng et al.   ANNALS OF NEUROLOGY

A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition

(2008) Neil E. Torbett et al.   BIOCHEMICAL JOURNAL

Reversal of learning deficits in a Tsc2 +/− mouse model of tuberous sclerosis

(2008) Dan Ehninger et al.   NATURE MEDICINE

PI3K pathway alterations in cancer: variations on a theme

(2008) T L Yuan et al.   ONCOGENE