Related Experiment Video

Updated: Feb 14, 2026

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
09:29

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

Published on: March 20, 2020

19.0K

Neomorphic ERα Mutations Drive Progression in Breast Cancer and Present a Challenge for New Drug Discovery

Donald P McDonnell1, John D Norris1, Ching-Yi Chang1

  • 1Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.

Cancer Cell
|February 14, 2018
PubMed

Insights

Estrogen receptor alpha mutants drive endocrine therapy resistance in breast cancer. These mutants exhibit new, disease-promoting activities that contribute to tumor development.

Area of Science:

  • Oncology
  • Molecular Endocrinology
  • Genetics

Background:

  • Endocrine therapy resistance is a major challenge in breast cancer treatment.
  • Estrogen receptor alpha (ER) signaling is a key driver of many breast cancers.
  • Mutations in ER are increasingly recognized as a mechanism of resistance.

Purpose of the Study:

  • To investigate the functional consequences of clinically relevant estrogen receptor alpha mutants.
  • To understand how these mutants contribute to endocrine therapy resistance and tumor pathogenesis.

Main Methods:

  • Functional assays were performed on specific ER alpha mutants.
  • Analysis of neomorphic activities associated with mutant ER alpha.

Main Results:

  • Clinically important ER alpha mutants display significant neomorphic (new) activities.
  • These neomorphic activities are relevant to breast cancer disease progression.

Conclusions:

  • Estrogen receptor alpha mutants actively contribute to breast cancer pathogenesis.
  • Targeting mutant ER alpha may offer new therapeutic strategies for resistant breast cancer.

More Related Videos

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer07:45

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer

Published on: May 18, 2020

7.1K
Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells05:02

Modeling Brain Metastasis Via Tail-Vein Injection of Inflammatory Breast Cancer Cells

Published on: February 4, 2021

3.9K

Related Concept Videos

Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
12.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.9K
Mutations01:39

Mutations

Overview
94.7K
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.7K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
40.0K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
15.0K