2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.51 ERBB3-BCAR4 is a recurrent fusion in lung adenocarcinoma cases that lack other driver alterations

PP01.51 ERBB3-BCAR4 is a recurrent fusion in lung adenocarcinoma cases that lack other driver alterations

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This document details a clinical case study and associated research on the ERBB3-BCAR4 gene fusion in lung adenocarcinoma, particularly in cases lacking other driver mutations. A 40-year-old woman who has never smoked was diagnosed with metastatic lung adenocarcinoma, and genetic sequencing identified an ERBB3-BCAR4 fusion. Notably, this specific genetic alteration was detected via the UW-Oncoplex DNA panel-based NGS, and no other driver mutations were found in this patient, echoing patterns in other reported cases. The study highlights the uniqueness of ERBB3-BCAR4 as a recurrent fusion in such cancer cases, especially among non-smokers and tumors negative for other well-known mutations.<br /><br />Research included sequencing analyses from four patients with the ERBB3-BCAR4 fusion, demonstrating high expression of both ERBB3 and BCAR4 genes. The study suggests the fusion is functional, with RNA sequencing indicating it likely does not signal through an EGFR or HER2 heterodimer, based on its low EGFR/ERBB2 activity score.<br /><br />Experiments on cell lines embellish these findings: overexpressing ERBB3-BCAR4 in normal lung epithelial and cancer cell lines showed varying growth advantages and resistance to ALK inhibition, evidenced by resistance to lorlatinib treatment. The research proposes potential future steps, like exploring lorlatinib resistance assays and testing drugs like patritumab deruxtecan as therapeutic options.<br /><br />Overall, the ERBB3-BCAR4 fusion signifies a novel oncogenic driver in certain lung adenocarcinoma subtypes, paving the way for potential targeted treatments. Further investigations are suggested to confirm its role and utility in therapeutic developments.

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Kevin Levine

Keywords

ERBB3-BCAR4

lung adenocarcinoma

gene fusion

non-smokers

genetic sequencing

oncogenic driver

targeted treatment

lorlatinib resistance

patritumab deruxtecan

NGS panel