Related Experiment Video

Updated: Jan 28, 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

18.8K

Precise targeting of POLR2A as a therapeutic strategy for human triple negative breast cancer

Jiangsheng Xu1,2,3, Yunhua Liu4,5, Yujing Li4,5

  • 1Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.

Nature Nanotechnology
|February 27, 2019
PubMed

Insights

Triple negative breast cancer (TNBC) lacks targeted therapies. Researchers identified POLR2A as a vulnerability, developing pH-activated nanoparticles delivering POLR2A siRNA (siPol2) to inhibit tumor growth in TP53-mutated TNBC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Nanotechnology

Background:

  • Triple-negative breast cancer (TNBC) has poor outcomes and no targeted therapies.
  • TP53 gene mutations are common in TNBC, leading to loss of its tumor-suppressive function.
  • The lack of targeted treatments for TNBC underscores the need for novel therapeutic strategies.

Purpose of the Study:

  • To identify novel therapeutic targets in TNBC.
  • To develop an effective delivery system for targeted gene silencing.
  • To evaluate the therapeutic potential of inhibiting POLR2A in TNBC.

Main Methods:

  • In silico analysis to identify collateral vulnerabilities in TNBC.
  • Design and synthesis of pH-activated nanoparticles for siRNA delivery.
  • In vitro and in vivo studies to assess the efficacy of POLR2A siRNA (siPol2) delivered via nanoparticles.

Main Results:

  • POLR2A was identified as a collateral vulnerability target in TNBC.
  • pH-activated nanoparticles successfully delivered siPol2 to cancer cells, enhancing cytosolic delivery.
  • siPol2-loaded nanoparticles significantly reduced tumor growth in TNBC models with TP53 alterations.

Conclusions:

  • Targeting POLR2A represents a promising therapeutic strategy for TNBC.
  • pH-responsive nanoparticles offer an effective platform for targeted siRNA delivery in TNBC.
  • This approach shows potential for treating TNBC patients with TP53 genomic alterations.

More Related Videos

Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System10:51

Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System

Published on: April 23, 2021

4.6K
Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 26, 2014

24.0K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.9K
Scalar and Vector Triple Products01:06

Scalar and Vector Triple Products

Two vectors can be multiplied using a scalar product or a vector product. The resultant of a scalar product is scalar, while with vector products, the resultant is a vector. These rules of the scalar or vector product between two vectors can be applied to multiple vectors to obtain meaningful combinations. The scalar triple product is the dot product of a vector with the cross product of two vectors.
The scalar triple product is the dot product of a vector with the cross product of two vectors....
4.4K
Uncertainty in Measurement: Accuracy and Precision03:37

Uncertainty in Measurement: Accuracy and Precision

Scientists typically make repeated measurements of a quantity to ensure the quality of their findings and to evaluate both the precision and the accuracy of their results. Measurements are said to be precise if they yield very similar results when repeated in the same manner. A measurement is considered accurate if it yields a result that is very close to the true or the accepted value. Precise values agree with each other; accurate values agree with a true value. 
100.9K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.5K
Positive, Negative, and Zero Work00:58

Positive, Negative, and Zero Work

Work is done on an object when energy is transferred to the object. In other words, work is done when a force acts on a body that undergoes a displacement from one position to another. By definition, the work done by a force is the integral of the force with respect to the displacement along its path. Forces can vary as a function of position, and displacements can occur along various paths between two points. The magnitude of a force multiplied by the cosine of the angle that the force makes...
22.1K
Therapeutic Index01:13

Therapeutic Index

The therapeutic index of a drug is a key parameter in pharmacology that quantifies the relative safety of a drug by calculating the ratio between the dose that causes toxicity in half the population (50%) to the dose that proves to be effective for half the population (50%). It provides a spectrum of doses for a particular drug ranging from effective to potentially toxic. To illustrate, consider an anticoagulant agent like warfarin. It possesses a narrow window within its therapeutic index to...
6.7K