ROR1 (Receptor Tyrosine Kinase Like Orphan Receptor 1)

The computational results reveal that kinases like AKT1, ROR1, and ROR2, and non-kinase targets like UBC, RPS6, CDH1, AR, and SMAD3, are the most promising candidates. All screened compounds showed varying strong interacting profiles, with Ellagic Acid and Erioflorin standing out as potent candidates against critical targets in metastatic breast cancer.

Methylation analyses indicated complex regulation of CTSS and TNFRSF19. WFDC1, RHOC, and GSTM4 exhibit therapeutic potential, while MFGE8, CTSS, TNFRSF19, and IL1RAP predict risk and prognosis, providing insights for precision diagnosis and treatment.

In conclusion, this study identifies ROR1 as a novel marker of aggressive cSCC, linked to poor differentiation, lymphatic spread and perineural invasion. ROR1 holds potential both as a prognostic biomarker and as a therapeutic target, encouraging future exploration of ROR1-directed therapies in advanced cSCC.

Transcriptomic analysis indicated the potential involvement of ROR1 in the PI3K/AKT pathway. In general, these findings support [18F]AlF-NP1 and [68Ga]Ga-DP1 as promising noninvasive imaging agents for quantitative ROR1 visualization and personalized cancer therapy.

Cholesterol was found to promote the assembly of ROR1, and our results point to the transmembrane domain as the region where cholesterol exerts this regulatory effect. Taken together, our results indicate that ROR1 self-assembles in human cells; however, unlike other RTKs, this process is not stabilized by ligand binding but is instead facilitated by membrane cholesterol.

Here, we developed and characterized a phage-derived single-chain fragment variable (scFv) against a highly specific ROR1 region and generated scFv-derived chimeric monoclonal antibodies and anti-ROR1-CAR NK cells, which show anti-cancer efficacy against TNBC cells. Additionally, we found TGF-β inhibition using either small-molecule inhibitors or CRISPR-Cas9-edited NK cells could further enhance ROR1-targeting therapy persistence and efficacy in controlling TNBC tumor growth.

High ROR1 expression predicts shorter overall survival, particularly in early-stage and Type I EC, supporting its potential as a prognostic biomarker. Given the retrospective single-center design, limited sample size, and absence of molecular validation, further multicenter and mechanistic studies are warranted to confirm these findings.

To our knowledge, BIQO-9 represents the first ROR1/PI3Kα/BRD4 multi-target inhibitor with therapeutic potential in NSCLC. Moreover, the combination of BIQO-9 and Gefitinib offers a promising novel strategy for NSCLC treatment.

Clinical implementation of the CLL assay revealed 12 out of 77 (16%) CLL PB patient samples demonstrating a small population of plasmablasts. Plasmablasts normally exist in peripheral blood at levels detectable by flow cytometry MRD assays and may be a potential confounder in the identification of MRD in CLL.

In vitro and in vivo, ConvAD CAR T cells targeting combinations of ROR1, CD19, and CD20 prevent lymphoma outgrowth across models of stable antigen expression as well as single- or dual antigen loss, and benchmark superior to both single-antigen specific and bispecific CAR T cells. The ConvAD CAR platform thus addresses a medical need by offering an effective strategy for multi-antigen targeting, counteracting antigen escape.

These findings underscore the need for careful patient selection and risk assessment when prescribing tofacitinib. Further prospective studies are warranted to confirm these associations and explore the underlying mechanisms.

Using an anti-receptor tyrosine kinase-like orphan receptor 1 (ROR1) mAb as a proof-of-concept anchoring arm and an array of affinity-modulated variants of the anti-epidermal growth factor receptor (EGFR) GA201 mAb as active arms, we show in vitro conditional engagement and elimination of double-positive human NCI-H358 non-small cell lung cancer cells over single-positive, non-target NCI-H358.ROR1.KO cells by affinity-modulated TriMab TCEs...Lastly, we demonstrate that the TriMab modality exhibits a favorable developability profile and mAb-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, this work presents a generalizable approach to utilizing the TriMab modality by leveraging avidity effects and molecular geometry to achieve conditional AND-gated dual TAA-targeting with a significantly improved TI.