DLK1 (Delta Like Non-Canonical Notch Ligand 1)

Our findings suggest that elevated DLK1 expression in HCC is linked to advanced BCLC stages, big tumor sizes and poor prognosis in HCC patients after surgical resection. DLK1 seems to serve as a valuable biomarker and may be a candidate for therapeutic targeting of HCC pending further validation.

Furthermore, DLK overexpression by an adenovirus vector enhanced colony formation and suppressed the cisplatin- and taxol-induced death in human ovarian cancer cells. Collectively, these results suggest that targeting DLK1 may represent a potential therapeutic strategy to improve outcomes in recurrent ovarian cancer following chemotherapy.

The NOTCH pathway converges with the WNT pathway. Differential expression of the immunohistochemical markers of these pathways helps in the semiquantitation of various epithelial components, guides adjuvant treatment, and patient prognostication.

The mRNA and protein expression of NCoR1 and DLK1 in siRNA-mediated transfection supported the reduced proliferation in endometrial cancer cells by interfering with certain pathways like Notch, MAPK, SWI/SNF, and NF-κB, which have crucial roles in the grade of receptor to the histone remodeling. With these findings, the study recommends exploring the possible role and interactions of NCoR1 and DLK1, signaling pathways that favor the progression of endometrial cancer.

Collectively, our findings provide critical insight into MPNST tumorigenesis and support prospective studies evaluating the utility of DLK1 tissue and serum levels in augmenting diagnosis, risk assessment and therapeutic stratification in the setting of NF1-PNST.

Furthermore, we found that there are m6A modification sites in DLK1 mRNA, and the expression of m6A modified DLK1 mRNA increased after RA treatment, and YTHDF2 regulates the expression level of DLK1, and the expression of YTHDF2-bound DLK1 mRNA decreased after RA treatment. These suggest that YTHDF2 may regulate the proliferation and apoptosis of NB cells in a cell line-dependent manner by binding to the m6A modification site of DLK1 mRNA to affect its expression, and YTHDF2 and DLK1 are potential therapeutic targets for patients with NB.

CBA-1205 was well tolerated, showing no severe toxicity in patients with advanced or recurrent solid tumors. The favorable safety profile and indications of potential activity support further investigation in Parts 2 and 3 of this Phase I study to evaluate the safety, tolerability, and preliminary efficacy of CBA-1205.

Finally, we observed that DLK1+ cells (those expressing DLK1) in both cell lines exhibited significantly higher levels of stemness markers compared to DLK1- cells (those lacking DLK1 expression). These findings underscore DLK1's role in enhancing the stemness phenotype, providing valuable insights into MTC progression and resistance and suggesting potential therapeutic implications.

ADCT-701, a DLK1-targeting antibody-drug conjugate (ADC), shows potent and specific cytotoxicity in DLK1-expressing neuroblastoma xenograft models. Since high DLK1 expression is found in several adult and pediatric cancers, our study demonstrates the utility of a proteogenomic approach and credentials DLK1 as an immunotherapeutic target.

This study presents DLK1 as a novel biomarker in ACC with opportunities for use in the diagnosis, prognosis and longitudinal follow up of patients. DLK1, a marker of adrenocortical stem cells, is re-expressed in ACC, is measurable in patients' serum and is associated with increased malignancy.

Pharmacological intervention targeting DNA methylation combined with histone deacetylation restored ncRNA expression. These results contribute to the understanding of the epigenetic mechanisms controlling the DLK1-DIO3 region in thyroid cancer, highlighting the combined role of DNA methylation and histone marks in regulating the locus' expression.

Therefore, the DLK1/DIO3 locus is an essential determinant of FoxM1-dependent cell proliferation during β-catenin-driven liver tumorigenesis. Targeting the DLK1-WRE enhancer to silence the DLK1/DIO3 locus might thus represent an interesting therapeutic strategy to restrict tumor growth in primary liver cancers with CTNNB1 mutations.