WCLC 2025 - Posters & ePosters-P2.02.26 Establishment of a HER2 Overexpressing Lung Squamous Cell Carcinoma Cell Line Sensitive to Targeted and Cytotoxic Therapies

P2.02.26 Establishment of a HER2 Overexpressing Lung Squamous Cell Carcinoma Cell Line Sensitive to Targeted and Cytotoxic Therapies

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This study reports the establishment and characterization of a novel lung squamous cell carcinoma (LSCC) cell line overexpressing HER2, derived from a 47-year-old male patient with a heavy smoking history. LSCC accounts for roughly 30% of non-small cell lung cancers and typically lacks effective targeted therapies, especially regarding HER2, which is more commonly studied in lung adenocarcinomas.<br /><br />The newly developed cell line was characterized by a 36-hour doubling time and successfully grew in vivo as xenografts in nude mice. Immunostaining confirmed LSCC markers, with p63 positivity and TTF-1/PD-L1 negativity. Whole genome sequencing revealed a high HER2 copy number (190) and elevated c-MET expression. RT-PCR confirmed the expression of HER2 and c-MET at the mRNA level.<br /><br />Drug sensitivity assays demonstrated that the cell line was responsive to conventional LSCC chemotherapies cisplatin, carboplatin, and paclitaxel, but not to pemetrexed. Importantly, HER2-targeted agents trastuzumab deruxtecan (an antibody-drug conjugate) and afatinib (a tyrosine kinase inhibitor) inhibited cell proliferation with low IC50 values, indicating sensitivity. Trastuzumab alone had limited effect.<br /><br />Clinically, the patient received surgery followed by adjuvant cisplatin and vinorelbine chemotherapy but experienced recurrence managed with radiation and systemic therapy including carboplatin, nab-paclitaxel, and pembrolizumab immunotherapy, achieving stable disease over 23 maintenance cycles. The patient’s clinical response to carboplatin and paclitaxel paralleled the in vitro drug sensitivity observed.<br /><br />In conclusion, this HER2-overexpressing LSCC cell line provides a valuable model demonstrating that HER2-targeted therapies may have translational potential in LSCC, a subtype lacking established HER2-directed treatments. Agents such as trastuzumab deruxtecan and afatinib represent promising future treatment options for HER2-positive LSCC patients experiencing disease progression.

Asset Subtitle

Satoshi Suzuki

Meta Tag

Speaker Satoshi Suzuki

Topic Tumor Biology – Preclinical Biology

Keywords

lung squamous cell carcinoma

LSCC cell line

HER2 overexpression

non-small cell lung cancer

drug sensitivity

trastuzumab deruxtecan

afatinib

c-MET expression

chemotherapy response

HER2-targeted therapy