PTK7-targeted cancer therapies: molecular understanding and clinical developments

PTK7, as a pseudo-kinase, has its abnormal expression closely related to the progression and prognosis of various malignant tumors. PTK7 is not a typical inhibitory oncogenic target but rather more like an enriched surface recognition on tumor cells, which can be used as drug delivery target and for degradation-based therapeutic strategies.

This review summarizes PTK7's molecular structural traits and transcriptional/post-transcriptional regulatory mechanisms, as well as its critical role in tumorigenesis. It evaluates PTK7's clinical significance across cancers, discusses PTK7-guided molecular imaging applications, and critically assesses emerging targeted strategies, including antibody-drug conjugates (ADCs), aptamer-drug conjugates (ApDCs), and aptamer-based lysosome-targeting chimeras (LYTACs).

The therapeutic value of PTK7 is attributed to its high surface expression, efficient internalization, and tumor-preferential distribution. Among available PTK7-targeted modalities, aptamer-based ApDC and LYTAC platforms fit well with PTK7's biological features via convenient synthesis and customizable modification, despite being limited by unsatisfactory serum stability and suboptimal in vivo pharmacokinetics at present. Given its high tumor expression, PTK7-targeted agents hold great potential for combination with immune checkpoint inhibitors, and further biomarker-based combinatorial designs are essential to advance its clinical translation.