Related Experiment Video

Updated: Jan 27, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
11:34

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers

Published on: December 5, 2017

13.1K

HER2-positive breast cancer: new therapeutic frontiers and overcoming resistance

Sonia Pernas1, Sara M Tolaney2

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medical Oncology-Breast Cancer Unit, Institut Catala d'Oncologia (ICO)-H.U. Bellvitge-IDIBELL, Barcelona, Spain.

Therapeutic Advances in Medical Oncology
|March 27, 2019
PubMed

Insights

Anti-HER2 therapies improve survival for HER2-positive breast cancer. New strategies are needed to overcome resistance and further enhance patient outcomes by understanding tumor biology and microenvironment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Anti-HER2 therapies have significantly improved survival for HER2-positive breast cancer patients.
  • Resistance to anti-HER2 therapy is a major challenge, leading to eventual disease progression in metastatic settings.
  • Understanding resistance mechanisms, tumor heterogeneity, and the tumor microenvironment is crucial for developing new treatments.

Purpose of the Study:

  • To review current strategies for overcoming resistance to anti-HER2 therapies in HER2-positive breast cancer.
  • To explore novel therapeutic approaches, including dual-blockade, antibody-drug conjugates, and new targeted agents.
  • To discuss the potential of combining anti-HER2 therapies with other agents like immune checkpoint inhibitors and CDK4/6 inhibitors.

Main Methods:

  • Literature review of preclinical and clinical studies on HER2-positive breast cancer treatment and resistance.
  • Analysis of emerging therapeutic strategies targeting HER2 signaling and resistance pathways.
  • Evaluation of combination therapies involving anti-HER2 agents with other targeted or immunomodulatory drugs.

Main Results:

  • Several novel anti-HER2 therapies, including antibody-drug conjugates and tyrosine kinase inhibitors, are under development.
  • Combination strategies involving anti-HER2 therapy with immune checkpoint inhibitors, CDK4/6 inhibitors, and PI3K/AKT/mTOR inhibitors show promise in clinical trials.
  • These approaches aim to enhance efficacy, overcome resistance, and potentially allow for treatment de-escalation.

Conclusions:

  • Continued research into resistance mechanisms and tumor biology is essential for advancing HER2-positive breast cancer treatment.
  • Novel anti-HER2 therapies and combination strategies offer potential for improved patient outcomes.
  • Future directions include optimizing targeted therapies and exploring de-escalation strategies to minimize toxicity and cost.
Keywords:
HER2-positivebreast cancerdrug–antibody conjugatesnew anti-HER2 therapiesnovel combinationsresistancetyrosine kinase inhibitors

More Related Videos

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model09:29

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

Published on: March 20, 2020

18.8K
Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers06:02

Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers

Published on: February 20, 2017

7.9K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K
Bioavailability Enhancement: Determination and Conceptual Approaches in Overcoming Bioavailability Problems01:22

Bioavailability Enhancement: Determination and Conceptual Approaches in Overcoming Bioavailability Problems

Body:Bioavailability is a critical pharmacological concept that measures the extent and rate at which an active drug ingredient or therapeutic moiety enters the systemic circulation, remaining unchanged. It's a pivotal factor in determining a drug's efficacy and safety.The Biopharmaceutics Classification System (BCS) plays an essential role in drug development by categorizing drugs into four classes based on their solubility and permeability. This classification aids in understanding drug...
200
Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
24.7K
Position-effect Variegation02:32

Position-effect Variegation

In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
7.0K
Resistivity01:22

Resistivity

When a voltage is applied to a conductor, an electrical field is generated, and charges in the conductor feel the force due to the electrical field. The current density that results depends on the electrical field and the properties of the material. In some materials, including metals at a given temperature, the current density is approximately proportional to the electrical field. In these cases, the current density can be modeled as:
4.4K
Resistance01:19

Resistance

When a current moves through any conductor, the conductor causes some level of difficulty for the current to flow. The measure of that difficulty is known as the resistance of the material and is represented by R. Every material has its own resistance. In the case of conductors, heat is emitted whenever a current passes through them. Resistance depends on the resistivity of the material. Resistivity is a characteristic of the material used to fabricate electrical components, whereas the...
5.7K