Simultaneously, when STAT6 siRNA entered M2-TAMs by UMND, proliferation, migration, invasion and EMT in LUSC cells could be inhibited via the transforming growth factor-β1 (TGF-β1) pathway. Therefore, our results confirm that UMND is an ideal siRNA delivery strategy, revealing its potential to inhibit M2-TAMs polarization and ultimately treat LUSC.

P1, N=9, Terminated, Codiak BioSciences | N=30 --> 9 | Trial completion date: Apr 2024 --> May 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2023 --> May 2023; Company Bankruptcy

HSP110 is an essential protein for PMBL and cHL cell survival, through its interaction with STAT6 and its requirement for STAT6 phosphorylation. HSP110 is a cargo protein of XPO1 which is also required for STAT6 phosphorylation. HSP110 inhibitor and selinexor have a synergistic effect in reducing tumour growth, suggesting that this combination could be a promising new therapeutic strategy for PMBL and cHL.

The addition of anti-PD-1 further enhanced systemic antitumor responses. These results provide a pre-clinical rationale for the pursuit of an alternative therapeutic approach for patients with immune-resistant NSCLC.

In the mouse model, Sun suppressed the expression of CD206 and Ki67, simultaneously inhibiting the polarization of JAK1-STAT6 signaling. Sunitinib can suppress the M2 polarization of macrophages to exert the anti-HCC effect, which is its another anticancer mechanism.

P1b/2, N=3, Completed, Uma Borate | Recruiting --> Completed | N=80 --> 3

P1a, N=177, Completed, Sumitomo Pharma Oncology, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Jun 2022 | Trial primary completion date: Dec 2022 --> Jun 2022

Our study suggests that STAT6 activation plays an essential role in the development of Ph+ ALL and may be a potential therapeutic target in Ph+ ALL. Video abstract.

The combination of TP-0903 and decitabine was additive in vitro, and in vivo significantly prolonged median survival compared to single-agent treatments in mice xenografted with HL-60 (vehicle, 46 days; decitabine, 55 days; TP-0903, 63 days; combination, 75 days) or MV4-11 (R248W) (51 days; 62 days; 81 days; 89 days) (p < 0.001). Together, these results provide scientific premise for the clinical evaluation of TP-0903 in combination with decitabine in TP53 mutant AML.

Finally, combining the xCT inhibitor erastin with an anti-PDL1 antibody was more potent in inhibiting lung cancer progression. Therefore, suppression of xCT may overcome resistance to cancer immunotherapy.

The cytotoxic effects by mCRPs knock-down were potentiated in the cells co-treated with doxorubicin (Dox). In addition, STAT3, STAT6, and p38 MAPK inhibitors, including C188-9, AS1517499 and SB203580 effectively reduced the expression of CD46 in the treated colon cells, associated with increased cell apoptosis and LDH release. Further study with mouse model revealed that mCRPs knockdown by mCRPs-shRNA significantly reduced colon cancer growth, associated with increased expression of Bax, cleaved caspase-3 and C5b-9 deposition, but reduced expression of Bcl-2, IL-6 and IL-1beta in tumor tissues of nude mice transplanted with SW620 cells. Thereby, mCRPs expression in human colon cancer cells were upregulated by STAT3/STAT6/p38 MAPK signaling and mCRPs knockdown reduced colon cancer growth in mice through inducing tumor cell apoptosis.

We further demonstrated that IL4 potently promoted steroid synthesis. Our results indicate that IL4 induces HSD3B1 expression via multiple signaling pathways in HT-29 cells and may play a role in the regulation of steroid synthesis.