The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options

PROTAC targeted protein degraders: the past is prologue

(2022) Miklós Békés et al.   NATURE REVIEWS DRUG DISCOVERY

Abstract OT2-11-09: Lidera breast cancer: A phase III adjuvant study of giredestrant (GDC-9545) vs physician’s choice of endocrine therapy (ET) in patients (pts) with estrogen receptor-positive, HER2-negative early breast cancer (ER+/HER2- EBC)

(2022) Aditya Bardia et al.   CANCER RESEARCH

Abstract PD13-08: First-in-human safety and activity of ARV-471, a novel PROTAC® estrogen receptor degrader, in ER+/HER2- locally advanced or metastatic breast cancer

(2022) Erika Hamilton et al.   CANCER RESEARCH

Abstract OT2-11-05: SERENA-6: A Phase III study to assess the efficacy and safety of AZD9833 (camizestrant) compared with aromatase inhibitors when given in combination with palbociclib or abemaciclib in patients with HR+/HER2- metastatic breast cancer with detectable ESR1m who have not experienced disease progression on first-line therapy

(2022) François-Clément Bidard et al.   CANCER RESEARCH

Abstract OT2-11-01: EMBER-3: A randomized phase 3 study of LY3484356, a novel, oral selective estrogen receptor degrader vs investigator’s choice of endocrine therapy of either fulvestrant or exemestane, in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer previously treated with endocrine-based therapy

(2022) Komal Jhaveri et al.   CANCER RESEARCH

Nonviral Delivery Systems of mRNA Vaccines for Cancer Gene Therapy

(2022) Yusi Wang et al.   Pharmaceutics

A phase 1a/b trial of imlunestrant (LY3484356), an oral selective estrogen receptor degrader (SERD) in ER-positive (ER+) advanced breast cancer (aBC) and endometrial endometrioid cancer (EEC): Monotherapy results from EMBER.

(2022) Komal L. Jhaveri et al.   JOURNAL OF CLINICAL ONCOLOGY

Adjuvant study of amcenestrant (SAR439859) versus tamoxifen for patients with hormone receptor-positive (HR+) early breast cancer (EBC), who have discontinued adjuvant aromatase inhibitor therapy due to treatment-related toxicity (AMEERA-6).

(2022) Thomas Meyskens et al.   JOURNAL OF CLINICAL ONCOLOGY

Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial

(2022) Francois-Clement Bidard et al.   JOURNAL OF CLINICAL ONCOLOGY

Neoadjuvant giredestrant (GDC-9545) plus palbociclib (P) versus anastrozole (A) plus P in postmenopausal women with estrogen receptor–positive, HER2-negative, untreated early breast cancer (ER+/HER2– eBC): Final analysis of the randomized, open-label, international phase 2 coopERA BC study.

(2022) Peter A. Fasching et al.   JOURNAL OF CLINICAL ONCOLOGY

211MO Giredestrant (GDC-9545) vs physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): Primary analysis of the phase II, randomised, open-label acelERA BC study

(2022) M. Martin Jimenez et al.   ANNALS OF ONCOLOGY

212MO AMEERA-3, a phase II study of amcenestrant (AMC) versus endocrine treatment of physician’s choice (TPC) in patients (pts) with endocrine-resistant ER+/HER2− advanced breast cancer (aBC)

(2022) S.M. Tolaney et al.   ANNALS OF ONCOLOGY

Phase I Study of Elacestrant (RAD1901), a Novel Selective Estrogen Receptor Degrader, in ER-Positive, HER2-Negative Advanced Breast Cancer

(2021) Aditya Bardia et al.   JOURNAL OF CLINICAL ONCOLOGY

Small-Molecule Degraders beyond PROTACs—Challenges and Opportunities

(2021) Johanna M. Kastl et al.   SLAS Discovery

LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation

(2021) Green Ahn et al.   Nature Chemical Biology

PROTAC: An Effective Targeted Protein Degradation Strategy for Cancer Therapy

(2021) Si-Min Qi et al.   Frontiers in Pharmacology

Novel Mechanisms of Molecular Glue-Induced Protein Degradation

(2021) Shanique Alabi   BIOCHEMISTRY

A Phase I Study of LSZ102, an Oral Selective Estrogen Receptor Degrader, with or without Ribociclib or Alpelisib, in Patients with Estrogen Receptor–Positive Breast Cancer

(2021) Komal Jhaveri et al.   CLINICAL CANCER RESEARCH

acelERA Breast Cancer (BC): Phase II study evaluating efficacy and safety of giredestrant (GDC-9545) versus physician’s choice of endocrine monotherapy in patients (pts) with estrogen receptor-positive, HER2-negative (ER+/HER2-) locally advanced or metastatic breast cancer (LA/mBC).

(2021) Miguel Martin et al.   JOURNAL OF CLINICAL ONCOLOGY

Safety and activity of single-agent giredestrant (GDC-9545) from a phase Ia/b study in patients (pts) with estrogen receptor-positive (ER+), HER2-negative locally advanced/metastatic breast cancer (LA/mBC).

(2021) Komal L. Jhaveri et al.   JOURNAL OF CLINICAL ONCOLOGY

SERENA-4: A phase 3 comparison of AZD9833 (camizestrant) plus palbociclib, versus anastrozole plus palbociclib, for patients with ER-positive, HER2-negative advanced breast cancer who have not previously received systemic treatment for advanced disease.

(2021) Seock-Ah Im et al.   JOURNAL OF CLINICAL ONCOLOGY

AMEERA-1: Phase 1/2 study of amcenestrant (SAR439859), an oral selective estrogen receptor (ER) degrader (SERD), with palbociclib (palbo) in postmenopausal women with ER+/ human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC).

(2021) Sarat Chandarlapaty et al.   JOURNAL OF CLINICAL ONCOLOGY

GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer

(2021) Jun Liang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Lysosome-targeting chimeras evolve

(2021) Joshiawa Paulk   Nature Chemical Biology

A phase I dose escalation and expansion study of the next generation oral SERD AZD9833 in women with ER-positive, HER2-negative advanced breast cancer.

(2020) Erika Paige Hamilton et al.   JOURNAL OF CLINICAL ONCOLOGY

Lysosome-targeting chimaeras for degradation of extracellular proteins

(2020) Steven M. Banik et al.   NATURE

Translational strategy using multiple nuclear imaging biomarkers to evaluate target engagement and early therapeutic efficacy of SAR439859, a novel selective estrogen receptor degrader

(2020) Laurent Besret et al.   EJNMMI Research

Discovery of AZD9833, a Potent and Orally Bioavailable Selective Estrogen Receptor Degrader and Antagonist

(2020) James S. Scott et al.   JOURNAL OF MEDICINAL CHEMISTRY

Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2–negative advanced breast cancer: final overall survival results from SOLAR-1

(2020) F. André et al.   ANNALS OF ONCOLOGY

The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor–Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy—MONARCH 2

(2019) George W. Sledge et al.   JAMA Oncology

Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer

(2019) Dennis J. Slamon et al.   NEW ENGLAND JOURNAL OF MEDICINE

Abstract PD5-10: A first-in-human phase I study to evaluate the oral selective estrogen receptor degrader (SERD), GDC-0927, in postmenopausal women with estrogen receptor positive (ER+) HER2-negative metastatic breast cancer (BC)

(2018) MN Dickler et al.   CANCER RESEARCH

Structural and functional characteristics of oestrogen receptor β splice variants: Implications for the ageing brain

(2018) C. K. Kim et al.   JOURNAL OF NEUROENDOCRINOLOGY

Small Molecule Targeted Recruitment of a Nuclease to RNA

(2018) Matthew G. Costales et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

The Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer

(2018) Sasha M. Pejerrey et al.   Hormones & Cancer

Targeting EGFR/HER2/HER3 with a Three-in-One Aptamer-siRNA Chimera Confers Superior Activity against HER2 + Breast Cancer

(2018) Xiaolin Yu et al.   Molecular Therapy-Nucleic Acids

Synergistic targeting HER2 and EGFR with a bivalent aptamer-siRNA chimera efficiently inhibits HER2-positive tumor growth

(2018) LU XUE et al.   MOLECULAR PHARMACEUTICS

Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer

(2018) Nicholas C. Turner et al.   NEW ENGLAND JOURNAL OF MEDICINE

Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial

(2016) John F R Robertson et al.   LANCET

Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species

(2016) Jiří Wilhelm et al.   Oxidative Medicine and Cellular Longevity

The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer

(2016) James D Joseph et al.   eLife

Abstract 5053: Discovery of GDC-0810 a novel, non-steroidal selective estrogen receptor degrader with robust activity in pre-clinical models of endocrine-resistant breast cancer

(2015) James Joseph et al.   CANCER RESEARCH

Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study

(2015) Matthew J. Ellis et al.   JOURNAL OF CLINICAL ONCOLOGY

Oral Selective Estrogen Receptor Downregulators (SERDs), a Breakthrough Endocrine Therapy for Breast Cancer

(2015) Donald P. McDonnell et al.   JOURNAL OF MEDICINAL CHEMISTRY

The therapeutic role of fulvestrant in the management of patients with hormone receptor-positive breast cancer

(2014) Eva Ciruelos et al.   BREAST

Patient-reported symptoms and discontinuation of adjuvant aromatase inhibitor therapy

(2014) Kelley M. Kidwell et al.   CANCER

Modulation of BAG-1 Expression Alters the Sensitivity of Breast Cancer Cells to Tamoxifen

(2014) Hong Liu et al.   CELLULAR PHYSIOLOGY AND BIOCHEMISTRY

The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor   AF-2 is modified

(2014) S. Moverare-Skrtic et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Measuring Residual Estrogen Receptor Availability during Fulvestrant Therapy in Patients with Metastatic Breast Cancer

(2014) Michel van Kruchten et al.   Cancer Discovery

Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial

(2013) Stephen RD Johnston et al.   LANCET ONCOLOGY

Multiplex Genome Engineering Using CRISPR/Cas Systems

(2013) L. Cong et al.   SCIENCE

A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity

(2012) M. Jinek et al.   SCIENCE

Abstract S1-6: TAMRAD: A GINECO Randomized Phase II Trial of Everolimus in Combination with Tamoxifen Versus Tamoxifen Alone in Patients (pts) with Hormone-Receptor Positive, HER2 Negative Metastatic Breast Cancer (MBC) with Prior Exposure to Aromatase Inhibitors (AI).

(2011) T Bachelot et al.   CANCER RESEARCH

Special delivery: targeted therapy with small RNAs

(2011) D Peer et al.   GENE THERAPY

Incidence of Breast Cancer in the United States: Current and Future Trends

(2011) W. F. Anderson et al.   JNCI-Journal of the National Cancer Institute

Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer

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

New Insights into the Role of RNase L in Innate Immunity

(2010) Arindam Chakrabarti et al.   JOURNAL OF INTERFERON AND CYTOKINE RESEARCH

Activity of Fulvestrant 500 mg Versus Anastrozole 1 mg As First-Line Treatment for Advanced Breast Cancer: Results From the FIRST Study

(2009) John F.R. Robertson et al.   JOURNAL OF CLINICAL ONCOLOGY

Knocking down barriers: advances in siRNA delivery

(2009) Kathryn A. Whitehead et al.   NATURE REVIEWS DRUG DISCOVERY