JAK1 overexpression

PD-L1 was regulated mainly by the Jak2-Stat3/ MAPK-AP1 pathway, and besides the routine immunological functions, it supports OSCC survival, invasion, and therapy resistance. PD-L1 can be used as an indicator of severity and can be targeted along with Jak2-Stat3/ MAPK-AP1 for a better outcome OSCC.

These findings indicate that CXCL9 is a potential clinical biomarker of prognosis and immunotherapy efficacy for TNBC patients. Also, it stimulates JAK/STAT activity, which in turn modifies the tumor microenvironment.

These findings provide novel insights into the functional link between JAK1 LOF mutations and abnormal HIF pathway activation in EC and suggest that pharmacological inhibition of HIF1/2 represents a promising therapeutic strategy targeting JAK1-mutated ECs. Video Abstract.

AZD3759 is a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) on the basis of gefitinib and has been proven to enter the central nervous system...The present study aimed to compare the effects of AZD3759 and osimertinib on RA efficacy in NSCLC and explore the potential mechanism of action of AZD3759...The effects of AZD3759 on RA efficacy in PC-9 cells and in a brain metastasis animal model were significantly abolished by the overexpression of JAK1. Collectively, our results suggested that AZD3759 promoted RA antitumor effects in NSCLC by synergistic blockade of EGFR and JAK1.

JAK1 overexpression exhibited superior prognosis and immune infiltration in NSCLC.

Hyperactivation of JAK/STAT signaling and JAK1 overexpression was reversible as cerdulatinib withdrawal resulted in re-sensitization to the drug. Importantly, histone deacetylase inhibitor (HDACi) therapies were efficacious against cerdulatinib-resistant cells demonstrating a potential alternative therapy for use in TYK2-rearranged B-ALL patients who have lost response to JAKi treatment regimens.

These findings suggested that miR-20a-5p may act as a tumor suppressor in EC, in part through decreasing Jak1 expression. miR-20a-5p and Jak1 may therefore serve as potential therapeutic targets in EC.

Moreover, JAK1 was identified to be a target gene for miR‑583 in DU145 and PC3 cell lines and the expression levels of miR‑583 were revealed to be negatively correlated with JAK1 expression levels in PCa tissues. In conclusion, the findings of the present study suggested that miR‑583 may inhibit the proliferation and invasion of PCa cells by targeting JAK1, thus providing a novel therapeutic target for patients with PCa.

When we combine prednisolone treatment with selumetinib or ruxolitinib, we observe that ruxolitinib only synergizes with prednisolone in IL7-dependent steroid resistant PDX samples in the presence of IL7. Moreover, our data proposes that this synergistic effect may (in part) depend on the anti-MAPK-ERK effect downstream of JAK1/2-inhibition. Combined, our study strongly supports the enrollment of T-ALL patients in the current phase I/II SeluDex trial (NCT03705507), and contributes to the optimization and stratification of newly designed T-ALL treatment regimens.