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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 specific...

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Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
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Beyond amplification: precision approaches to targeting HER2.

Maxwell R Lloyd1, Mark D Pegram2, Seth A Wander3

  • 1Beth Israel Deaconess Medical Center Boston, MA United States.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 9, 2026
PubMed
Summary
This summary is machine-generated.

Combining HER2-targeted tyrosine kinase inhibitors with trastuzumab shows promise for metastatic breast cancer with HER2 mutations. This approach reveals molecular changes during treatment, aiding in understanding resistance and refining precision therapies.

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Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Metastatic breast cancer (MBC) with activating HER2 mutations presents a therapeutic challenge.
  • HER2-targeted therapies, including tyrosine kinase inhibitors (TKIs) combined with trastuzumab, are emerging as a treatment strategy.
  • Understanding the molecular landscape of response and resistance is crucial for optimizing treatment outcomes.

Purpose of the Study:

  • To investigate the efficacy of HER2-directed tyrosine kinase inhibitor combinations with trastuzumab in metastatic breast cancer patients with HER2 mutations.
  • To explore the molecular mechanisms of response and acquired resistance through correlative genomic analyses.
  • To identify patterns of molecular evolution during treatment to inform future therapeutic strategies.

Main Methods:

  • Retrospective analysis of patients with HER2-mutant metastatic breast cancer treated with HER2-directed TKI and trastuzumab combinations.
  • Correlative genomic profiling of tumor samples obtained at baseline and during treatment.
  • Analysis of on-target and downstream molecular alterations to identify response patterns and resistance mechanisms.

Main Results:

  • HER2-directed TKI and trastuzumab combinations demonstrated activity in both hormone receptor-negative and -positive HER2-mutant metastatic breast cancer.
  • Correlative genomics identified significant on-target and downstream molecular evolution throughout treatment.
  • Specific molecular alterations were associated with treatment response and the development of acquired resistance.

Conclusions:

  • Combination therapy with HER2-directed TKIs and trastuzumab is a viable strategy for HER2-mutant metastatic breast cancer.
  • Understanding treatment-induced molecular evolution is key to predicting response and overcoming resistance.
  • Further refinement of precision therapies targeting HER2 mutations in breast cancer is warranted.