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Updated: Oct 2, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
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HER2 targeted therapy in colorectal cancer: New horizons

Ali Abdulnabi Suwaidan1, David K Lau1, Ian Chau1

  • 1Gastrointestinal and Lymphoma Unit, Royal Marsden NHS Foundation Trust, London and Surrey SM2 5PT, United Kingdom.

Cancer Treatment Reviews
|March 1, 2022
PubMed

Insights

Human epidermal growth factor receptor 2 (HER2) amplification in metastatic colorectal cancer (mCRC) presents a resistance mechanism to anti-EGFR therapy. HER2-targeted therapies show significant clinical benefit in patients with HER2-amplified mCRC.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Metastatic colorectal cancer (mCRC) has low 5-year survival rates despite advances.
  • Chemotherapy is the primary treatment, with limited targeted therapy options.
  • Human epidermal growth factor receptor 2 (HER2) amplification occurs in ~5% of mCRC cases.

Purpose of the Study:

  • To review clinicopathological features of HER2 amplification and mutations in mCRC.
  • To examine HER2's role as a biomarker for anti-EGFR therapy resistance.
  • To summarize studies on HER2-targeted therapies in HER2-amplified mCRC.

Main Methods:

  • Review of preclinical, clinical, and translational studies.
  • Analysis of HERACLES-A, MyPathway, and DESTINY-CRC01 trial data.
  • Overview of clinicopathological characteristics of HER2 alterations in mCRC.

Main Results:

  • HER2 amplification is a mechanism of resistance to anti-EGFR therapy in mCRC.
  • HER2-targeted therapies demonstrate significant clinical benefit in HER2-amplified mCRC.
  • HER2 alterations impact treatment strategies and patient outcomes.

Conclusions:

  • HER2-targeted therapies are a promising treatment avenue for a subset of mCRC patients.
  • Understanding HER2 status is crucial for optimizing mCRC treatment.
  • Further research into HER2-targeted agents and resistance mechanisms is warranted.
Keywords:
Colorectal cancerHER2Human epidermal growth factor receptorPrecision medicineTargeted therapyctDNA

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