P1/2, N=12, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Aug 2025 --> Oct 2024

We also identified the distinct function of CD73 activity in adenocarcinoma and squamous cell carcinoma. Our findings indicated a role of CD73 in mediating NSCLC metastasis and propose it as a therapeutic target for NSCLC.

P1, N=0, Withdrawn, Washington University School of Medicine | N=36 --> 0 | Not yet recruiting --> Withdrawn

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2024 --> Aug 2025

To sum up, GAS6-AS1 promotes UBC progression through two distinct axes: the GAS6-AS1/miR-367-3p/MMP7 axis and the GAS6-AS1/PRC1/APC/Wnt/MMP7 axis, respectively. As a potential biomarker for UBC, GAS6-AS1 holds promising prospects for the diagnosis, treatment, and prognosis of UBC.

In the present manuscript, we review the current evidence regarding SSc pathogenesis and the role of the Gas6/TAM system in several human diseases, suggesting its likely contribution in SSc and highlighting areas where further research is necessary to fully comprehend the role of TAM receptors in this condition. Indeed, understanding the involvement of TAM receptors in SSc, which is currently unknown, could provide valuable insights for novel potential therapeutic targets.

Accordingly, we show that ligand bioavailability varies during the circadian cycle using RT-qPCR and immunoblots on retinal and retinal-pigment epithelial samples from control and beta5 integrin knockout mice where retinal phagocytosis is arrhythmic. Taken together, our results suggest that Gas6 and Protein S might both contribute to refine the acute regulation of MerTK in time for the daily phagocytic peak.

Importantly, pharmacological inhibition of either JAK1 by filgotinib or TAM kinases by UNC2025 sensitizes Ewing sarcoma to chemotherapy in vitro and in vivo. Excitingly, the TAM kinase inhibitor MRX-2843 currently in human clinical trials to treat AML and advanced solid tumors, enhances chemotherapy efficacy to further suppress Ewing sarcoma tumor growth in vivo. Our findings reveal an Ewing sarcoma chemoresistance mechanism with an immediate translational value.

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2025 --> Aug 2024 | Trial primary completion date: Feb 2025 --> Aug 2024

P1, N=36, Not yet recruiting, Washington University School of Medicine | Trial completion date: Jan 2034 --> Jun 2034 | Trial primary completion date: Jan 2029 --> Jun 2029

Results were corroborated using multivariate analysis. Our data suggest a protective role of Gas6 and its receptors in patients with MS and suitable severity disease biomarkers.

Batiraxcept effectively reduced serum GAS6 levels at 1-h post-treatment, resulting in trough levels below the limit of detection in all cases but one. In conclusion, the combination of batiraxcept and durvalumab was safe and tolerable but did not demonstrate anti-tumor activity in a heterogenous population of patients with recurrent PROC.

No abstract available

This effect occurs independent of any influence on microglial activation. This work therefore establishes that the remyelinative activity of GAS6 is dependent on Tyro3 and includes potentiation of oligodendrocyte numbers.

Remarkably, Nap-IR can synergistically enhance the anticancer effect of cisplatin against HO8910 ovarian tumors...Remarkably, Nap-IR can synergistically enhance the anticancer effect of cisplatin against HO8910 ovarian tumors. We anticipate that our Nap-IR can be applied in clinical ovarian cancer therapy in the near future.

Together, our findings elucidate that GAS6-AS1 directly binds to PCBP1, enhancing MCM3 expression and thereby promoting 5-FU resistance. GAS6-AS1 may serve as a robust biomarker and potential therapeutic target for combination therapy in CRC.

Soluble TAM-related proteins, mainly released from activated macrophages and hepatic stellate cells after hepatic deterioration, are proposed as early serum markers for disease progression. In conclusion, the TAM system is becoming an interesting pharmacological target in liver pathology and a focus of future biomedical research in this field.

In this review, we discuss MASH-associated HCC and the potential involvement of the Gas6/TAM system in disease development and progression. In addition, since therapeutic strategies for MASH and HCC are limited, we also speculate regarding possible future treatments involving the targeting of Gas6 or TAM receptors.

P1, N=36, Not yet recruiting, Washington University School of Medicine | Trial completion date: Aug 2033 --> Nov 2033 | Initiation date: Dec 2023 --> Mar 2024 | Trial primary completion date: Aug 2028 --> Nov 2028

Our results revealed that lncRNA GAS6-AS1 obtained from RNA-seq can be used as an independent risk factor for ESCC lymph node metastasis and an effective biomarker to predict, and that it was related to the growth and metastasis of ESCC. It may represent a new biomarker to aid in the assessment of the lymph node metastasis of ESCC.

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

The physiological significance of the Gas6/Axl-MICAL2 signaling pathway described here is supported by the marked gene expression correlation across a broad array of different cancers between MICAL2 and Axl and Gas6, as well as the coexpression of these genes and the known SRF/MRTF-A target transcripts. Overall, these data reveal a new link between Gas6/Axl and SRF/MRTF-A-dependent gene transcription and link MICAL2 as a novel effector of the Gas6/Axl signaling pathway.

P1/2, N=12, Active, not recruiting, M.D. Anderson Cancer Center | N=19 --> 12

Specifically, it was observed that the neuroprotective effect of EP was partially inhibited by GAS6 siRNA. In conclusion, these results suggest that EP treatment attenuates HR-induced oxidative stress injury in neuroblastoma cells via activating GAS6/Axl signaling.

Moreover, in vivo experiments confirmed the regulatory effects of corylin on these proteins, and corylin alleviated the symptoms of carbon tetrachloride-induced liver fibrosis in mice. These findings revealed that corylin has anti-inflammatory activity and inhibits HSC activation; thus, it presents as a potential adjuvant in the treatment of liver fibrosis.

Ozone reduces inflammation and alleviates gout pain by activating AMPK to up-regulate Gas6/MerTK/SOCS3 signaling pathway.

The GAS6/AXL pathway contributes to immunotherapy resistance in GC. Targeting this pathway may be a novel therapeutic strategy.

Finally, the in vitro findings were verified in vivo, which showed that FSH-induced proliferative and antiapoptotic effects in ovarian GCs were diminished after blocking GAS6/Axl using HIF-1α antagonist. These findings highlight a novel function of FSH in preserving GCs viability against hypoxic stress by activating the HIF-1a-GAS6-Axl-Akt pathway.

P1, N=36, Not yet recruiting, Washington University School of Medicine | Trial completion date: Apr 2033 --> Aug 2033 | Initiation date: Sep 2023 --> Dec 2023 | Trial primary completion date: May 2028 --> Aug 2028

P1b/2, N=72, Terminated, Aravive, Inc. | Trial completion date: Mar 2025 --> Aug 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Aug 2023; Due to business reasons

P3, N=366, Terminated, Aravive, Inc. | There was no detriment to overall survival. No new safety signals were identified.

P1b/2, N=34, Terminated, Aravive, Inc. | N=99 --> 34 | Trial completion date: Oct 2025 --> Aug 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2024 --> Aug 2023; Due to business reasons

P1, N=19, Active, not recruiting, University of Oklahoma | Trial primary completion date: Aug 2023 --> Jan 2024

Serum growth arrest-specific 6 levels were associated with prognosis in hepatocellular carcinoma patients. In early and intermediate-stage hepatocellular carcinoma patients who underwent transcatheter arterial chemoembolization, high growth arrest-specific 6 levels were associated with a high incidence of portal vein tumour thrombosis. Circulating growth arrest-specific 6 levels may be a useful prognostic marker in hepatocellular carcinoma patients.

However, silencing of GAS6 inhibited the neuroprotective effects of SIL. To sum up, these results showed that SIL may be a promising therapeutic agent for the treatment of ischemic stroke.

Gas 6 was not found to be an independent prognostic marker in pRCC. Future studies are warranted to determine if Gas 6 plays a role as prognostic marker or therapeutic target in pRCC.

Although Gas6 and Gas6/alb showed high diagnostic accuracy for the detection of HCC in comparison to chronic liver disease patients without cirrhosis (AUC 0.852, 0.868), they failed to discriminate between HCC in cirrhosis versus cirrhosis only. In conclusion, Gas6/alb shows a high accuracy to detect significant to advanced fibrosis and cirrhosis, and predicts severity of liver disease including CSPH.

Table: 1889P Conclusions BT + cabo demonstrated acceptable tolerability and promising efficacy in treatment-refractory ccRCC pts. BT + cabo will be further studied in a P3 trial of 2L+ ccRCC patients whose disease has progressed following IO and VEGF-TKI therapies.

Our findings indicate that GAS6-CAR-T-cell therapy may be effective for pancreatic cancers with low toxicity.

Taken together, our results suggest that Gas6 and its receptors, particularly Axl, might have a neuroprotective role and prognostic potential in MS.

Recently, multiple studies have begun to explore in depth the importance of the Gas6/AXL pathway as a potential tumor therapeutic target as well as its broad promise in immunotherapy; therefore, a timely review of the characteristics of the Gas6/AXL pathway and its value in tumor treatment strategies is warranted. This comprehensive review assessed the roles of Gas6 and AXL receptors and their associated pathways in carcinogenesis and cancer progression, summarized the impact of Gas6/AXL on the tumor microenvironment, and highlighted the recent research progress on the relationship between Gas6/AXL and cancer drug resistance.

Moreover, PRAME showed elevated expression in Axl-stratified HCC patients, which correlates with vascular invasion and lowered patient survival. (4) PRAME is a bona fide target of Gas6/Axl/ERK signaling linked to EMT and cancer cell invasion in HCC.