PTK7 (Protein Tyrosine Kinase 7)

While the panel showed promising performance for distinguishing MRD-positive from MRD-negative samples, the limited MRD-positive cohort size (n = 11) indicates that validation in larger MRD-focused studies is required before clinical implementation for treatment monitoring. This dPCR-based platform provides accessible, quantitative detection without requiring knowledge of clonal shifts or specific genomic landscape, offering potential advantages for resource-limited settings such as those represented in our Mexican pediatric cohort.

Furthermore, we explore how novel modalities like PROTACs and Antibody-Drug Conjugates (ADCs) are unlocking the "undrugged kinome," including targets like TNIK, PTK7, and PAK4, which were previously inaccessible. Finally, we propose that future success lies in combinatorial strategies integrating these next-generation kinase inhibitors with ADCs and immunotherapies to dismantle therapeutic resistance.

The efficacy of MBL-LYTACs in cancer therapy has been validated in two tumor xenograft models, with PD-L1 and EGFR as targets. Overall, this study establishes a robust and adaptable framework for targeted receptor degradation, expanding therapeutic opportunities in cancer management.

Different types of family-based analyses together with in silico predictions are helpful to identify candidate genes and pathways for CRC predisposition.

Finally, a single aptamer-modified tFNA with an edge length of 17 bp presents the best tumor delivery efficacy and effective therapeutic performance when combined with either chemotherapy or immunotherapy. This study elucidates how controllable size and valence influence delivery efficacy and introduces optimized Apt-tFNA constructs as promising agents for enhancing targeted therapeutic outcomes.

[212Pb]Pb-TCMC-chOI-1 was efficiently produced and demonstrated PTK7 specificity and potent cytotoxic efficacy, confirmed through both in vitro and in vivo studies. This highlights the therapeutic potential of [212Pb]Pb-TCMC-chOI-1 for the treatment of metastatic HGSOC following IP administration.

Guided by both experimental data and statistical mechanics modeling, we designed superselective homobivalent ligands that effectively discriminated PTK7high CCRF-CEM cells ((2.5 ± 0.26) × 105 PTK7/cell) from PTK7low HEL cells ((1.0 ± 0.05) × 105 PTK7/cell) in both in vitro and in vivo models. This study provides new insights into the fundamental principles of homobivalent ligand-cell interactions and establishes a framework for designing superselective ligands for cancer diagnosis and therapy based on membrane antigen density.

It maintained robust performance even under challenging conditions of low PTK7 expression, siRNA-mediated knockdown, or paclitaxel-induced suppression...With its remarkable potential for early cancer screening, real-time molecular tracking, and personalized therapeutic development, our platform represents a significant leap forward in molecular diagnostics. This study exemplifies the transformative power of electron-mediated proximity labeling, offering a promising avenue for advancing precision medicine and molecular biology.

The generalizability and versatility of predicted aptamer-protein structure directed covalent aptamer design strategy was further proven by tuning the nucleobase attached diazirine warhead of sgc8c to SF installed to backbone PS and by attaining covalent SL1 variants bearing backbone derivatized SF that can cross-link with its target c-Met. Our approach provides a proof-of-principle platform for converting conventional noncovalent aptamers into covalent counterparts through model-guided placement of reactive warheads, supplemented by systematic experimental validation, thereby achieving irreversible target intervention with therapeutic potential beyond the reach of noncovalent aptamers.

Furthermore, leveraging the multi-port design, we implemented an OR-AND logic gate system to achieve on-demand cell targeting and broad-spectrum cell killing. This nanoplatform provides a paradigm for manipulating cellular interactions through Boolean integration of cell-intrinsic markers and microenvironmental cues, advancing the development of precision cancer immunotherapy.

STSs express multiple target genes relevant for ADC treatment and expression varies between and within the pathological types. This comprehensive ADC target landscape, based on the largest molecular epidemiology study in STS, should help clinicians and drug developers for further evaluation of ADCs across STS types.

Efficacy studies in various cancer types with PTK7 overexpression showed that Sgc8c-M effectively induces sustained tumor regression in cell line-derived and patient-derived xenografts, outperforming unconjugated MMAE, the chemotherapy drug paclitaxel, and a PTK7-targeted antibody-drug conjugate...It was, moreover, well tolerated in monkeys with no obvious accumulation following multiple administrations. These findings highlight the potential of Sgc8c-M as an effective antitumor agent and provide useful insights for the clinical translation of emerging ApDCs.