Abstract C040: Real-world characterization of PTK7, an oncofetal pseudokinase expressed in multiple solid tumors

Abstract Background: Protein tyrosine kinase 7 (PTK7), a pseudokinase involved in embryogenesis, is downregulated in normal adult tissues but expressed in tumor tissue. Previous studies using The Cancer Genome Atlas (TCGA) database demonstrated consistent upregulation of PTK7 expression in multiple solid tumor samples versus matched adjacent normal tissue. However, TCGA studies are limited by small sample sizes and overrepresentation of early-stage disease. This study aims to characterize PTK7 expression across a large population, spanning multiple tumor types and disease stages. Methods: Data from the real-world Tempus Database were analyzed for PTK7 mRNA expression. In non-small cell lung cancer (NSCLC), PTK7 expression was compared between epidermal growth factor receptor (EGFR)-mutant (mut) vs wild-type (wt) and programmed death-ligand 1 (PD-L1)–positive vs negative tumors in adenocarcinoma (AC) and squamous cell carcinoma (SCC). In ovarian serous carcinoma (OV) and lung AC, PTK7 expression was assessed by disease stage. Expression was quantified by log2(transcripts per million [TPM]+1); differences in expression were analyzed using the Wilcoxon rank test. Co-expression of PTK7 with other biomarkers was evaluated; correlations were assessed using Pearson’s correlation coefficient. Results: PTK7 expression was analyzed in tumors from 116,067 patients. Tumors with the highest median log2(PTK7 TPM+1) levels included endometrial AC (7.5; n=3341), high-grade serous OV (7.3; n=3558), salivary gland cancer (7.1; n=601); lung SCC (7.0; n=7,371), head and neck SCC (7.0, n=3349); lung AC (6.9; n=16,021), and cervical SCC (6.9; n=596). In NSCLC, PTK7 expression was higher in EGFRmut vs EGFRwt tumors (7.3 vs 6.7 in AC, p<0.05; 7.2 vs 7.0 in SCC, p<0.05) and similar between PD-L1–positive (6.8 vs 6.9) and –negative tumors (6.9 vs 7.0). Median PTK7 expression decreased slightly in stage I vs stage IV disease in lung AC (7.1 to 6.7), high-grade serous OV (7.2 to 7.1), and low-grade serous OV (7.3 to 7.0). In lung AC, PTK7 expression correlated most strongly with HER2 (correlation coefficient [R]=0.33, p<0.05) and FOLR1 (R=0.33, p<0.05); this was also true for OV but the correlations were more modest (HER2 R=0.28; FOLR1 R=0.17; both p<0.05). Conclusions: PTK7 is expressed across a variety of solid tumors, including in a large endometrial dataset. NSCLC and OC show robust PTK7 expression across histologic and molecular subtypes. PTK7 expression is uniform across PD-L1 subgroups, which may allow combination of PTK7-targeted therapy with immune-oncology (IO) agents, while providing an additional therapeutic target for patients with IO-refractory disease. PTK7 expression remains high across disease stages, with only a modest decline in metastatic lesions, supporting its relevance in early- and late-stage disease. Co-expression with existing ADC targets suggests potential for combination strategies and identification of distinct patient subsets. Taken together, these results support PTK7 as a promising therapeutic target that warrants further investigation. Citation Format: Ursula A. Matulonis, Fernanda B. Musa, Grace K. Dy, David J. Lennon, David Dornan, Ashwini B. Pai, Kathleen S. Keegan, Kathleen N. Moore. Real-world characterization of PTK7, an oncofetal pseudokinase expressed in multiple solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C040.