EPHA2 overexpression

In addition, EphA2 regulates intercellular communication and the microenvironment through interactions with other cytokines and receptors, further influencing cancer progression. The role of EphA2 in GI CRC and its underlying mechanisms provide us with new perspectives and potential therapeutic targets, which have important implications for future cancer treatment.

In addition, we showed that recovering EPHA2 expression via plasmid-induced overexpression of EPHA2 or schisandrin C, a natural product, could prevent regorafenib-induced cardiotoxicity. These findings demonstrated that regorafenib causes cardiomyocyte apoptosis and cardiac injury by reducing the expression of EPHA2 and schisandrin C could prevent regorafenib-induced cardiotoxicity by recovering EPHA2 expression, which provides a potential management strategy for regorafenib-induced cardiotoxicity and will benefit the safe application of regorafenib in clinic.

BCY18469 demonstrated high affinity, specific targeting of EphA2, a favorable biodistribution profile, and clearance through renal pathways. These findings underscore the potentially important role of bicyclic peptides in advancing radiotheranostic approaches and encourage additional translational research.

We further determined that EphA2 overexpression inhibited autophagy by activating the mTOR pathway and suppressing SVV replication. Taken together, these results indicate that SVV 3Cpro targets EphA2 for cleavage to impair its EphA2-mediated antiviral activity and emphasize the potential of the molecular interactions involved in developing antiviral strategies against SVV infection.

And Tc-HYNIC-PEG4-EPH-3 could specifically target EphA2-expressing tumors, particularly with a tumor-to-non-target (T/NT) ratio >4.7 excluding kidneys. As a result of excellent biodistribution and tumor targeting capability of Tc-HYNIC-PEG4-EPH-3, it might be a promising candidate drug for clinical diagnosis of EphA2-overexpressing tumors.

When antibody hSD5 was administered with gemcitabine, significantly improved effects on tumor growth inhibition were observed. Based on the efficacy of the IgG hSD5 antibodies, clinical administration of the hSD5 antibodies is likely to suppress tumors in patients with pancreatic cancer and abnormal activation or overexpression of EphA2 signaling.

P1, N=76, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2024 --> Apr 2025 | Trial primary completion date: Jul 2023 --> Apr 2025

EBV-miR-BART1-3p and BART18-5p were found to target the 3'-UTR of EphA2 and down-regulate its expression. Our results suggest that EBV may be involved in gastric cancer progression by targeting EphA2 through BART1-3p and BART18-5p.

Conclusions RAYZ-6114 and RAYZ-6283 are first-in-class, highly potent and selective macrocyclic peptide binders. Preclinical pharmacodynamic, pharmacokinetic, biodistribution and efficacy data demonstrated their potential for treatment of patients with EphA2-positive tumors.

In a mouse model of spontaneous metastasis, the ATOP EphA2 aptamer slowed primary tumor growth and significantly reduced the number of lung metastases. The EphA2 ATOP aptamer represents a promising candidate for the development of next-generation targeted therapies that provide safer and more effective treatment of EphA2-overexpressing tumors.

Our findings demonstrated that circRTTN mediated melanoma progression via regulating the miR-890/ EPHA2 axis.

This study identified the HCG11/miR-1297/EphA2 regulatory axis in SACC, which might provide novel therapeutic targets for SACC.

Also, anlotinib enhances the inhibitory effect of irradiation on mice. It is concluded that anlotinib inhibits EphA2 expression, thereby suppressing angiogenesis and resensitizing EC cells to radiotherapy, providing another perspective to overcome radioresistance in EC.

P1, N=76, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

This work demonstrates a novel mechanism of radiation resistance in medulloblastoma and identifies an epigenetic marker predictive of radiotherapy response. Based on these findings, we propose an epigenetically guided treatment approach targeting radiotherapy resistance in medulloblastoma patients.

Our study stresses that EPHA2 expression constitutes a potential prognostic factor for TNBC patients. Given the limited treatment options and poorer outcome that accompany the TNBC subtype, EPHA2 could also pose as a target for novel, more personalized, and effective therapeutic approaches for those patients.

P1, N=75, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2021 --> Jul 2024 | Trial primary completion date: Jul 2021 --> Jul 2023

Furthermore, Filamin A expression affected the subcellular localization of EphA2. This study suggests that Filamin A selectively promotes EphA2 S897 phosphorylation and plays an important role in glioblastoma cell proliferation.

Furthermore, dual luciferase reporter assay verified that miR-10b-5p was a target of EphA2, and the rescue experiment implied that transfection of pCMV-EphA2 or Si-EphA2 could reverse EphA2 expression and cell biological functions caused by miR-10b-5p overexpression or knockdown. miR-10b-5p reduced HCC cell proliferation but accelerate apoptosis by regulating EphA2, suggesting it has the potential to be a clinical target for HCC.

Our work demonstrates a novel mechanism of radiation resistance in medulloblastoma and identifies an epigenetic marker predictive of radiotherapy response. Based on these findings we propose an epigenetically guided personalized treatment approach to target radiotherapy resistance in medulloblastoma patients.

Circ_0062270 accelerated the progression of melanoma through regulating the miR-331-3p/EPHA2 axis, suggesting that circ_0062270 might be a novel potential therapeutic target for melanoma.

MK2206 (AKT inhibitor) and RAD001 (mTOR inhibitor) reversed the effect of EPHA2 overexpression on the biological behavior of Cal-27 cells. EPHA2 promotes the invasion and migration of Cal-27 human OSCC cells by enhancing the AKT/mTOR signaling pathway.

P1, N=75, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=40 --> 75 | Trial completion date: Jul 2020 --> Jul 2021 | Trial primary completion date: Jul 2020 --> Jul 2021

In contrast, BT5528 achieves prolonged toxin delivery to tumors, following transient exposure in plasma of less than one hour. A Phase I/II study of BT5528 in patients with solid tumors is ongoing, which will investigate if this PK novel, differentiated pharmacokinetic profile, unique to Bicycle toxin conjugates, gives rise to a favorable balance of efficacy and safety.

Inhibition of EphA2 by AWL-II-41-27, EphA2-specific tyrosine kinase inhibitor, or knock-down of EphA2 decreased mRNA and protein expression of cyclin-dependent kinase (CDK) 6 in CC cells, which increased cellular susceptibility to epirubicin (EPI), an anti-cancer chemotherapy drug...EphA2 protein expression was positively correlated with CDK6 protein expression, invasion depth, lymph node metastasis and clinicopathological stage (P < .05). This study demonstrates the oncogenic activity of EphA2 in vitro and in vivo, which provides insights into the relevant mechanisms that might lead to novel treatments for CC.

Our results revealed that miR-519a enhances radiosensitivity of NSCLC by inhibiting EphA2 expression. Moreover, miR-519a serves as a target for NSCLC treatment.