The protein tyrosine kinase-7 or PTK7 is a oncofetal transmembrane pseudokinase that has emerged as a potential therapeutic target for human tumors. PTK7 is involved in the modulation of the Wnt signaling pathway through interactions with other receptors, leading to targeted gene activation that regulates cell polarity, migration, and proliferation during early embryonic development.[1]
PTK7 has restricted expression in adult tissues and frequently overexpression in various cancers including lung, colorectal cancer, leukemia, neuroblastoma, hepatoma, ovarian cance, endometrial cancers, and linked to poor prognosis. This expression of PTK7 is stable across histologic subtype, disease stage and metastatic status, underscoring relevance in both early- and late-stage disease.
Based on this understanding, preclinical research and phase I clinical trials of novel, investigational agents aims at inhibiting PTK7 and inducing antitumoral effects.[1]
An analysis
Results from a real-world analysis of PTK7, released at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held October 22 – 26, 2025 in Boston, Massachusetts, characterized PTK7 expression and demonstrated that PTK7 is the third most highly expressed tumor marker among clinically validated after HER2 and HER3, present in ~70% of tumors. Furthermore, the analysts showed that the highest median PTK7 mRNA expression was observed in endometrial (7.4), ovarian (7.2), head and neck (7.1), non-small cell lung cancer (NSCLC) (6.9) and breast (6.7) tumors.
Finally, the analysis showed that the expression levels of PTK7 were comparable to or exceeding clinically validated and emerging ADC targets:
- Lung cancer: Comparable to HER2, HER3, Trop-2 and cMET.
- Ovarian cancer: Comparable to HER2 and FRα; markedly higher than CDH6, B7-H4 and CLDN6.
- Endometrial cancer: Comparable to Trop-2; markedly higher than FRα, B7-H4 and HER2
This large-scale RNA analysis of >157,000 tumor samples, nearly half from metastatic lesions, confirmed that PTK7 as one of the most broadly and highly expressed targets across solid tumors, reinforcing its potential as a clinically meaningful pan-tumor ADC target, and further support development of HWK-007 (Whitehawk Therapeutics), a PTK7-directed antibody-drug conjugates.[2]
The analysis was conducted as part of a previously announced collaboration between Whitehawk and Tempus AI, a technology company leading the adoption of AI to advance precision medicine.[2]
“These results emphasize the translational potential of PTK7 as a broadly expressed and stable target across solid tumors,” said Grace Dy, MD, Chief, Thoracic Oncology, Professor of Oncology, Department of Medicine, Roswell Park Comprehensive Cancer Center.
“By demonstrating consistent expression across histologies, disease stages and sample types, this analysis builds on the foundational rationale for developing next-generation ADCs that have the potential to reach a wide range of patients,” Dy added.
Development plan
HWK-007 is a PTK7-targeting ADC that leverages an advanced ADC technology platform which consists of a highly stable yet cleavable linker that delivers a Topoisomerase I (TOPO1) inhibitor payload. The developers plan to submit an Investigational New Drug (IND-) application to the U.S. Food and Drug Administration (FDA) for HWK-007 by year-end, with initial clinical evaluation planned in NSCLC, ovarian and endometrial cancers.
“These findings reinforce PTK7’s promise as one of the most compelling and underexplored ADC targets in oncology,” said Dave Lennon, PhD, President and Chief Executive Officer, Whitehawk Therapeutics.
“As the third most abundant tumor marker across all cancer patients – present in approximately 70% of solid tumors – the opportunity for HWK-007 has never been clearer. We believe we are well positioned to develop a differentiated ADC that could have a meaningful impact for the nearly 750,000 patients in the US with PTK7-expressing cancers,” Lennon concluded.
Reference
[1] Mottard K, Cokaiko J, Rogister B, Neirinckx V. Therapeutic targeting of the protein tyrosine kinase-7 in cancer: an overview. Oncologist. 2025 Aug 4;30(8):oyae290. doi: 10.1093/oncolo/oyae290. PMID: 39468753; PMCID: PMC12395136.
[2] 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.
[3] SEER Incidence Data, 1975-2022. National cancer Institute (NCI). Online. Last accesses on October 24, 2025.
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