PI3K/AKT/mTOR: role in breast cancer progression, drug resistance, and treatment

451PDPHASE I STUDY OF THE PI3Kα INHIBITOR BYL719, AS A SINGLE AGENT IN PATIENTS WITH ADVANCED SOLID TUMORS (AST)

(2017) D. Juric et al.   ANNALS OF ONCOLOGY

PIK3CAmutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab

(2016) S. Loibl et al.   ANNALS OF ONCOLOGY

A Phase I Study of the AKT Inhibitor MK-2206 in Combination with Hormonal Therapy in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer

(2016) C. X. Ma et al.   CLINICAL CANCER RESEARCH

Molecular Alterations and Everolimus Efficacy in Human Epidermal Growth Factor Receptor 2–Overexpressing Metastatic Breast Cancers: Combined Exploratory Biomarker Analysis From BOLERO-1 and BOLERO-3

(2016) Fabrice André et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase II Randomized Preoperative Window-of-Opportunity Study of the PI3K Inhibitor Pictilisib Plus Anastrozole Compared With Anastrozole Alone in Patients With Estrogen Receptor–Positive Breast Cancer

(2016) Peter Schmid et al.   JOURNAL OF CLINICAL ONCOLOGY

Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From BOLERO-2

(2016) Gabriel N. Hortobagyi et al.   JOURNAL OF CLINICAL ONCOLOGY

Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial

(2016) Ian E Krop et al.   LANCET ONCOLOGY

Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer

(2015) Giovanni Ciriello et al.   CELL

A Phase I Trial of BKM120 (Buparlisib) in Combination with Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer

(2015) C. X. Ma et al.   CLINICAL CANCER RESEARCH

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

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

Intrinsic Subtypes,PIK3CAMutation, and the Degree of Benefit From Adjuvant Trastuzumab in the NSABP B-31 Trial

(2015) Katherine L. Pogue-Geile et al.   JOURNAL OF CLINICAL ONCOLOGY

Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial

(2015) Sara A Hurvitz et al.   LANCET ONCOLOGY

PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor–positive breast cancer

(2015) Ana Bosch et al.   Science Translational Medicine

INPP4B: the New Kid on the PI3K Block

(2015) Irina U. Agoulnik et al.   Oncotarget

Abstract DDT02-01: Discovery of GDC-0032: A beta-sparing PI3K inhibitor active against PIK3CA mutant tumors.

(2014) Alan G. Olivero et al.   CANCER RESEARCH

Tumor Genetic Analyses of Patients with Metastatic Renal Cell Carcinoma and Extended Benefit from mTOR Inhibitor Therapy

(2014) M. H. Voss et al.   CLINICAL CANCER RESEARCH

First-in-Human Phase I Study of Pictilisib (GDC-0941), a Potent Pan-Class I Phosphatidylinositol-3-Kinase (PI3K) Inhibitor, in Patients with Advanced Solid Tumors

(2014) D. Sarker et al.   CLINICAL CANCER RESEARCH

Stand Up to Cancer Phase Ib Study of Pan-Phosphoinositide-3-Kinase Inhibitor Buparlisib With Letrozole in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer

(2014) Ingrid A. Mayer et al.   JOURNAL OF CLINICAL ONCOLOGY

Mutational Analysis of PI3K/AKT Signaling Pathway in Tamoxifen Exemestane Adjuvant Multinational Pathology Study

(2014) Vicky S. Sabine et al.   JOURNAL OF CLINICAL ONCOLOGY

Biomarker Analyses in CLEOPATRA: A Phase III, Placebo-Controlled Study of Pertuzumab in Human Epidermal Growth Factor Receptor 2–Positive, First-Line Metastatic Breast Cancer

(2014) José Baselga et al.   JOURNAL OF CLINICAL ONCOLOGY

Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial

(2014) Fabrice André et al.   LANCET ONCOLOGY

Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer

(2014) Nikhil Wagle et al.   NEW ENGLAND JOURNAL OF MEDICINE

Gain of Interaction with IRS1 by p110α-Helical Domain Mutants Is Crucial for Their Oncogenic Functions

(2013) Yujun Hao et al.   CANCER CELL

Impact of PTEN Protein Expression on Benefit From Adjuvant Trastuzumab in Early-Stage Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer in the North Central Cancer Treatment Group N9831 Trial

(2013) Edith A. Perez et al.   JOURNAL OF CLINICAL ONCOLOGY

Discovery of 2-{3-[2-(1-Isopropyl-3-methyl-1H-1,2–4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): A β-Sparing Phosphoinositide 3-Kinase Inhibitor with High Unbound Exposure and Robust in Vivo Antitumor Activity

(2013) Chudi O. Ndubaku et al.   JOURNAL OF MEDICINAL CHEMISTRY

Development of PI3K inhibitors: lessons learned from early clinical trials

(2013) Jordi Rodon et al.   Nature Reviews Clinical Oncology

Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies

(2013) A. B. Hanker et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Investigational drug MLN0128, a novel TORC1/2 inhibitor, demonstrates potent oral antitumor activity in human breast cancer xenograft models

(2012) Yesim Gökmen-Polar et al.   BREAST CANCER RESEARCH AND TREATMENT

Abstract 917: AZD2014, a dual mTORC1 and mTORC2 inhibitor is differentiated from allosteric inhibitors of mTORC1 in ER+ breast cancer

(2012) Sylvie M. Guichard et al.   CANCER RESEARCH

mTOR Signaling in Growth Control and Disease

(2012) Mathieu Laplante et al.   CELL

The p110  and p110  isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis

(2012) T. Utermark et al.   GENES & DEVELOPMENT

Randomized Phase II Trial of Everolimus in Combination With Tamoxifen in Patients With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer With Prior Exposure to Aromatase Inhibitors: A GINECO Study

(2012) Thomas Bachelot et al.   JOURNAL OF CLINICAL ONCOLOGY

Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

(2012) Antonio C. Wolff et al.   JOURNAL OF CLINICAL ONCOLOGY

Comprehensive molecular portraits of human breast tumours

(2012) Daniel C. Koboldt et al.   NATURE

Conditional activation of Pik3ca H1047R in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations

(2012) W Yuan et al.   ONCOGENE

Physiological Levels of Pik3caH1047R Mutation in the Mouse Mammary Gland Results in Ductal Hyperplasia and Formation of ERα-Positive Tumors

(2012) Anjali Tikoo et al.   PLoS One

Oncogenic mutations mimic and enhance dynamic events in the natural activation of phosphoinositide 3-kinase p110  (PIK3CA)

(2012) J. E. Burke et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Genome Sequencing Identifies a Basis for Everolimus Sensitivity

(2012) G. Iyer et al.   SCIENCE

Cooperation between Pik3ca and p53 Mutations in Mouse Mammary Tumor Formation

(2011) J. R. Adams et al.   CANCER RESEARCH

Phosphatidylinositol 3-Kinase and Antiestrogen Resistance in Breast Cancer

(2011) Todd W. Miller et al.   JOURNAL OF CLINICAL ONCOLOGY

Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer

(2011) José Baselga et al.   NEW ENGLAND JOURNAL OF MEDICINE

ER -Dependent E2F Transcription Can Mediate Resistance to Estrogen Deprivation in Human Breast Cancer

(2011) T. W. Miller et al.   Cancer Discovery

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

Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor–positive human breast cancer

(2010) Todd W. Miller et al.   JOURNAL OF CLINICAL INVESTIGATION

Cancer-derived mutations in the regulatory subunit p85  of phosphoinositide 3-kinase function through the catalytic subunit p110 

(2010) M. Sun et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor-positive breast cancer

(2010) S. Loi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phosphatidyl-inositol-3-kinase alpha catalytic subunit mutation and response to neoadjuvant endocrine therapy for estrogen receptor positive breast cancer

(2009) Matthew J. Ellis et al.   BREAST CANCER RESEARCH AND TREATMENT

Evidence that Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor that Inhibits PI3K Signaling

(2009) Christina Gewinner et al.   CANCER CELL

Somatic Mutations in p85α Promote Tumorigenesis through Class IA PI3K Activation

(2009) Bijay S. Jaiswal et al.   CANCER CELL

PIK3CA and PIK3CB Inhibition Produce Synthetic Lethality when Combined with Estrogen Deprivation in Estrogen Receptor-Positive Breast Cancer

(2009) R. J. Crowder et al.   CANCER RESEARCH

PIK3CA Mutation Associates with Improved Outcome in Breast Cancer

(2009) K. Kalinsky et al.   CLINICAL CANCER RESEARCH

Inhibition of Mammalian Target of Rapamycin Is Required for Optimal Antitumor Effect of HER2 Inhibitors against HER2-Overexpressing Cancer Cells

(2009) T. W. Miller et al.   CLINICAL CANCER RESEARCH

Tenets of PTEN Tumor Suppression

(2008) Leonardo Salmena et al.   CELL

Dose- and Schedule-Dependent Inhibition of the Mammalian Target of Rapamycin Pathway With Everolimus: A Phase I Tumor Pharmacodynamic Study in Patients With Advanced Solid Tumors

(2008) Josep Tabernero et al.   JOURNAL OF CLINICAL ONCOLOGY

Antitumor Activity of Rapamycin in a Phase I Trial for Patients with Recurrent PTEN-Deficient Glioblastoma

(2008) Tim F Cloughesy et al.   PLOS MEDICINE