EGFR and HER2 exon 20 insertions in solid tumours: from biology to treatment

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are key targets in several cancers.
• Activating mutations like EGFR exon 19 deletions and HER2 amplification predict response to targeted therapies.
• However, EGFR/HER2 exon 20 insertions show limited sensitivity to existing treatments.

Purpose of the Study:

• To review the prevalence, biology, and detection of EGFR and HER2 exon 20 insertions.
• To analyze the response of these mutations to current targeted therapies and immunotherapies.
• To highlight emerging therapeutic strategies for tumors with these alterations.

Main Methods:

• Literature review of studies on EGFR and HER2 exon 20 insertions.
• Analysis of mutation prevalence across various cancer types.
• Evaluation of treatment responses and emerging therapeutic approaches.

Main Results:

• EGFR and HER2 exon 20 insertions occur across multiple cancer types, including lung, breast, and colorectal cancers.
• These insertions are structurally distinct, leading to reduced sensitivity to current EGFR/HER2 inhibitors and antibodies.
• Current targeted therapies and immunotherapies show limited efficacy against these specific mutations.

Conclusions:

• EGFR and HER2 exon 20 insertions represent a significant challenge in cancer therapy due to resistance to existing treatments.
• Understanding the unique biology of these mutations is crucial for developing effective therapies.
• Novel therapeutic approaches are under development to overcome resistance and improve outcomes for patients with these alterations.