Esophageal Squamous Cell Carcinoma

Moreover, HMGA1 was highly expressed in ESCC tissues and positively correlated with PARP1 levels as well as poor prognosis in ESCC patients. Taken together, these findings reveal a mechanistic link between HMGA1 and PARP1 in regulating cell responses to DNA damage and suggest that targeting HMGA1 could be a promising strategy to increase cancer cell sensitivity to olaparib.

combined acetazolamide (AZA) to target carbonic anhydrase IX (CA IX) with two tyrosine-derived Mn(II)-ethylenediaminetetraacetic acid chelates (TyEDTA) on a rigid triazine (TA) scaffold...Using CA IX as a biomarker of hypoxia, Cao et al. have thus illustrated a practical strategy for the development of novel imaging probes for specific regions of hypoxia in a tumor of interest.

The results of our study highlight the prognostic significance of URDEGs in ESCC, suggesting that they may serve as useful biomarkers and therapeutic targets. Future research should focus on clinical validation and the development of targeted therapies to improve the outcomes of patients with ESCC.

These data revealed the potential role of DGS/X-ray co-therapy in controlling ESCA resistance to radiotherapy by inhibiting the USP14/YAP1 axis, providing a candidate strategy for ESCA treatment.

TRACeR-based bispecific T cell engagers and chimeric antigen receptor T cells exhibit on-target killing of tumor cells with high efficacy in the low nanomolar range. Our platform empowers the development of broadly applicable MHC I-targeting molecules for research, diagnostic and therapeutic applications.

In animal studies, RFC4 knockdown, either alone or in combination with radiation therapy, effectively suppressed the growth of xenograft tumors. These findings highlight the potential of targeting RFC4 to overcome radioresistance by modulating the DNA damage response in ESCC, offering promising therapeutic avenues for ESCC patients.

P1/2, N=105, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Trial completion date: Sep 2022 --> Dec 2026 | Trial primary completion date: Sep 2022 --> Dec 2025

P2, N=80, Recruiting, Lisata Therapeutics, Inc. | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Mar 2026

P=N/A, N=500, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting | Initiation date: Aug 2024 --> Dec 2024

In pyroptosis, LRRFIP2 and FLII which can inhibit pyroptosis increasingly binding to MST1. Our findings delineate potential mechanisms through which MST1 and its interactomes regulate cell death, paving the way for further investigation to validate and consolidate these observations.

Importantly, patients with high proportions of hsCAFs showed poor survival and a worse response to chemotherapy. In summary, these findings identify a hsCAF subpopulation generated by interplay between cancer cells and CAFs under hypoxic conditions that promotes ESCC stemness and reveal targeting hsCAFs as an effective therapeutic strategy against chemotherapy-resistant ESCC.

RBM15 enhances tumor-infiltrating CD4+ T Cell abundance in ESCC by regulating PLOD3. Two new independent prognostic factors, PLOD3 and RBM15, may be useful in predicting the prognosis of ESCC.

P1, N=6, Recruiting, West China Hospital | Initiation date: Dec 2024 --> Aug 2024

P2, N=40, Completed, Wuhan University | Recruiting --> Completed | Trial completion date: Dec 2023 --> Nov 2024 | Trial primary completion date: Aug 2023 --> Nov 2024

Mechanistic investigations revealed that circCREBBP, modified by m6A, interacted with IGF2BP3 and competitively bound to it, thereby reducing MYC mRNA stability. This study identified circCREBBP as a new m6A-modified circRNA and confirmed the METTL3/IGF2BP3/circCREBBP/MYC axis as a potential therapeutic target in enhancing radiosensitivity in ESCC.

Our data highlight the imaging manifestations associated with ICI-related pulmonary toxicity and describe the dynamics of the corresponding circulating markers. Although our results reveal that dynamic monitoring of PLR and PMR as well as the levels of CD4+T and CD8+T cells may predict the risk of ICI-P, further investigations are needed to elucidate the underlying molecular and biological mechanisms for better management of ICI-P.

P=N/A, N=856, Active, not recruiting, The First Affiliated Hospital of Henan University of Science and Technology

A low Mito-score before NAC had a significant survival impact in ESCC patients, especially in those with advanced disease. Mitochondrial status might be associated with tumor aggressiveness and responsiveness to NAC, thereby possibly affecting the survival outcomes of ESCC patients.

This selective activity allows HCFe to significantly elevate ROS production and exert cytotoxic effects, especially against cisplatin-resistant esophageal squamous cell carcinoma (ESCC) cells and their xenografts in female mice when combined with cisplatin. These findings underscore HCFe's potential as a crucial component in multimodal cancer therapy, notably in augmenting chemotherapy efficacy.

Overall, our findings not only indicate that KDM1A is a promising target for ESCC patients at early stages but also provide novel mechanistic insights into its spatial regulation of STING-associated anti-tumor immunity in sTILs to drive the oncogenic processes in ESCC. The translation of these findings will ultimately guide more appropriate combinations of spatial immunotherapies with KDM1A inhibitors to improve the overall survival of specific subgroups in ESCC.

This study identified three key genes that predict chemoradiotherapy sensitivity and prognosis and are involved in multiple tumor-related biological processes in ESCC. These findings provide predictive biomarkers for chemoradiotherapy response and support the development of individualized treatment strategies for ESCC patients.

P2, N=112, Recruiting, The First Affiliated Hospital of Zhengzhou University

P=N/A, N=28, Recruiting, University of California, San Francisco | Trial completion date: Nov 2026 --> Nov 2027 | Trial primary completion date: Dec 2024 --> Dec 2025

Overall, this data proposes lnc191 as a key driver during the development of ESCC and reveals the participation of the activated GRP78/ERK/MAPK axis in the ESCC progression mediated by lnc191. These findings indicate the potential of lnc191 as a promising diagnostic biomarker and therapeutic target in ESCC.

P=N/A, N=20, Not yet recruiting, First Affiliated Hospital of Ningbo University

P1, N=890, Active, not recruiting, Daiichi Sankyo Co., Ltd. | Recruiting --> Active, not recruiting

The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.37±0.11 vs 1.00±0.01 (P=0.037), and after radiotherapy the expression of γ-H2AX increased. Oct4 is involved in the regulation of epithelial-mesenchymal transformation of esophageal squamous cell carcinoma, which promotes the proliferation, migration, and radioresistance of esophageal squamous cell carcinoma.

circ-TTC17 promoted ESCC cell growth, metastasis and inhibited autophagy-mediated radiosensitivity by miR-145-5p/SIRT1 axis.

Circ_0096710 upregulates ADAM10 via mediating miR-1294 expression so as to accelerate the occurrence of ESCC, suggesting that circ_0096710 may be a potential therapeutic target for ESCC.

Yet, these effects were blocked by further silencing of PATZ1. In summary, this research demonstrates that SMURF1 activates β-catenin signaling by suppressing the PATZ1/CCNG2 axis, thereby promoting the progression of ESCC.

P1, N=6, Recruiting, West China Hospital | Initiation date: Oct 2023 --> Dec 2024

P2, N=64, Recruiting, Northwestern University | Not yet recruiting --> Recruiting | Initiation date: May 2025 --> Nov 2024

P2, N=35, Recruiting, National Taiwan University Hospital | Not yet recruiting --> Recruiting | Initiation date: May 2024 --> Aug 2024

The overexpression of STC1 enhances the migration, invasion and proliferation of ESCC cells, and is significantly associated with poor prognosis in ESCC patients. Therefore, STC1 may serve as a promising prognostic factor and could also be a potential target for ESCC-specific therapy.

P2, N=52, Recruiting, Shanghai Chest Hospital

P=N/A, N=400, Recruiting, Fujian Medical University Union Hospital

We established a DRG-lncRNA prognostic model that can be used to predict the prognosis, tumor mutation burden, immune cell infiltration, and drug sensitivity of ECSS patients. The results of this study provide valuable insights into the understanding of ESCC and provide valuable assistance for the individualized treatment of ESCC patients.

Additionally, inhibition of EVA1B attenuated the expansion and recruitment of MDSCs within the immune microenvironment based upon the reduction in the percentage of CD11b+Gr-1+ immunosuppressive MDSCs as well as the expression of MDSC expansion stimulators (S100A8, S100A9, Arg-1, and VEGF). Collectively, our findings unveiled the contribution of high expression of EVA1B to ESCC progression and MDSCs expansion and recruitment, indicating that targeted suppression of EVA1B may be a potential treatment choice for ESCC patients.

Compared with chemotherapy alone, Sintilimab or camrelizumab plus chemotherapy seemed to achieve the best progression-free survival (hazard ratio = 0.56, 95% CI 0.46-0.68)...Nivolumab plus ipilimumab resulted in a relatively lower incidence of adverse events of grade ≥3 than other regimens. The combination of immune checkpoint inhibitors (ICIs) with chemotherapy provided a high probability of more effective treatment in comparison with chemotherapy alone for patients with advanced ESCC. Toripalimab and sintilimab plus chemotherapy were ranked as providing the highest OS and PFS benefit in the first-line setting, respectively.

This finding opens new possibilities for targeted therapies, offering hope for improved patient outcomes. Thus, this study underscored the pivotal role of HOX gene dysregulation in ESCC and classified HOXA7 as a potential prognostic biomarker in this tumor.

P1, N=20, Completed, Sichuan University | Not yet recruiting --> Completed | Trial completion date: Sep 2023 --> Oct 2024

P2, N=70, Completed, BeiGene | Active, not recruiting --> Completed | Trial completion date: May 2026 --> Oct 2024