Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GI-101 as a Single Agent or in Combination With Pembrolizumab, Lenvatinib or Local Radiotherapy in Advanced Solid Tumors

ABSTRACT: The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A as a single agent or in combination with pembrolizumab, lenvatinib or local radiotherapy (RT) over a range of advanced and/or metastatic solid tumors.

DISEASE(S): Vulvar Cancer,Carcinoma,Sarcoma,Vaginal Cancer,Vaginal Neoplasms,Cervical Cancer,Melanoma,Urinary Bladder Cancer,Urinary Bladder Neoplasms,Merkel Cell Carcinoma,Carcinoma, Merkel Cell,Neoplasms,Carcinoma, Squamous Cell,Vulvar Neoplasms,Squamous Cell Carcinoma Of Head And Neck,Metastatic Solid Tumor,Microsatellite Stable Colorectal Carcinoma,Non-small Cell Lung Cancer,Advanced Solid Tumor,Colorectal Neoplasms,Head And Neck Squamous Cell Carcinoma,Renal Cell Carcinoma,Esophageal Squamous Cell Carcinoma

PROVIDER: 2384499 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

RNA-seq analysis of lenvatinib-sensitive and lenvatinib-resistant tumor tissues from a subcutaneous HCC mouse model

Project description:To investigate the molecular mechanisms underlying acquired resistance to lenvatinib in hepatocellular carcinoma (HCC), we established a lenvatinib-resistant mouse model using H22 cell-based subcutaneous xenografts. Tumor tissues were collected from lenvatinib-sensitive (H22-NR) and lenvatinib-resistant (H22-LR) mice. We performed RNA-sequencing to identify differentially expressed genes and signaling pathways that mediate lenvatinib resistance. Comparative gene expression profiling analysis between the NR and LR groups was conducted to screen for key drivers of drug resistance.

2026-04-23 | GSE328515 | GEO

The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma

Project description:To understand the role of HIF1a in lenvatinib resistance, we conducted label-free quantitative proteome analysis in both control and lenvatinib resistance cell lines. This analysis revealed changes in the proteome due to the lenvatinib resistance, providing a valuable reference for further investigations.

2024-08-20 | PXD054805 | Pride

Syntaxin-6 mediated autophagy confers lenvatinib resistance in hepatocellular carcinoma

Project description:Lenvatinib is the first-line therapy for inoperable HCC. However, intrinsic and acquired drug resistance occurs during the treatment period. Autophagy is an adaptive response that favors tumor survival under stress. In the present study, we aim to reveal the unknown autophagic engagement in lenvatinib resistance. Lenvatinib-resistant HCC cell lines and xenograft mouse HCC models were established to identify the key regulator of lenvatinib resistance in HCC. By in vitro functional restoration assays and autophagic flux detection, we demonstrated that the Syntaxin-6 (STX6) -mediated autophagy induced lenvatinib resistance of HCC cells. Mechanistically, Co-immunoprecipitation assay and mass spectrometry indicated that the interactions of STX6 with Beclin1, VTI1A, and VAMP3 facilitated autophagy, leading to the lenvatinib resistance. Additionally, STX6 enhanced the ability of proliferation, migration, and invasion of HCC in vitro and in vivo. Clinically, STX6 expression was significantly elevated in HCC tissues compared to it in para-tumor tissues. High STX6 expression predicted poor outcomes for patients following resection. Moreover, high expression of STX6 displayed low preventive efficacy of lenvatinib as a postoperative adjuvant treatment for HCC patients with a high risk of recurrence. Collectively, we identified that STX6-mediated autophagy was a pivotal determinant of lenvatinib resistance in HCC, providing a potential target to overcome lenvatinib resistance for HCC patients.

2025-12-01 | GSE285575 | GEO

Lenvatinib recruits cytotoxic GZMK+CD8 T cells in hepatocellular carcinoma

Project description:Lenvatinib targets multiple oncogenic kinases including vascular endothelial growth factor receptors (VEGFRs) and showed longer median progression-free survival than sorafenib, the only approved treatment for >10 years. With the successful combination therapy of anti-PD-L1 pembrolizumab and anti-VEGF bevacizumab for advanced HCC as well as encouraging experimental findings, lenvatinib was also expected to enhance anti-tumor effects by combining anti-PD-1 pembrolizumab compared to lenvatinib alone; however, the phase III clinical trial failed to show their synergetic survival benefits, highlighting the need for elucidating its mode of action in human HCC specimens after lenvatinib treatment. We performed multi-layer transcriptome analyses of surgically resected human HCC samples after lenvatinib treatment as a neo-adjuvant therapy using RNA-sequencing. Molecular pathway analyses and immunohistochemistry revealed that VEGF-mediated aberrant vascularity and cytotoxic GZMK+CD8 T cells infiltration were significantly improved in lenvatinib-treated HCC; however, the majority of these cytotoxic T cells were trapped in the intratumor fibrotic stroma, suggesting that lenvatinib-treated HCC is in the so-called excluded condition. Excluded tumors are generally believed to be less responsive to immune checkpoint inhibitors, which might be the reason the combination therapy failed to show the additive benefits.

2023-08-08 | GSE223201 | GEO

Single cell RNA sequencing of immune cells from lenvatinib-resistant mouse HCC model after lenvatinib or combined lenvatinib and CDK4/6 inhibitor palbociclib treatment

Project description:We used single-cell RNA sequencing (scRNA seq) to elucidate the alterations of tumor microenvironment upon combined treatment of lenvatinib and palbociclib (combo).

2023-09-27 | GSE218010 | GEO

RNA Sequencing of HCC cells after lenvatinib, gefitinib, and combination treatment

Project description:Using a kinome-centred CRISPR/Cas9 genetic screen, we identify here that inhibition of the epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer cells. We found that the combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effect in HCC cell lines that express EGFR in vitro and of xenografted HCC cell lines or patient-derived HCC tumours in mice. Herre, we analyzed the different transcriptome profiling of HCC cells treated with DMSO, lenvatinib, gefitinib, and lenvatinib plus gefitinib by RNA-sequencing.

2021-07-22 | GSE157905 | GEO

GI-SINE Analyses

Project description:GI-SINE Analyses

| PRJNA966999 | ENA

Identification of genes regulated by GIGANTEA (GI), the CYCLING DOF FACTORS (CDFs) and the GI-CDF module

Project description:Plants monitor and integrate temperature, photoperiod and light quality signals to respond to continuous changes in their environment. The GIGANTEA (GI) protein is central in diverse signaling pathways, including photoperiodic, sugar and light signaling pathways, stress responses and circadian clock regulation. Previously, GI was shown to activate expression of the key floral regulators CONSTANS (CO) and FLOWERING LOCUS T (FT) by facilitating degradation of a family of CYCLING DOF FACTOR (CDF) transcriptional repressors. However, whether CDFs are implicated in other processes regulated by GI remains unclear. We investigated the contribution of the GI-CDF module to traits that depend on GI. Transcriptome profiling indicated that mutations in GI and the CDFs have antagonistic effects on expression of a wider set of genes than CO and FT, whilst other genes are regulated by GI independently of the CDFs. Detailed expression studies followed by phenotypic assays showed that the CDFs function downstream of GI to control responses to freezing temperatures and growth, but are not necessary for proper clock function. Thus GI-mediated regulation of CDFs contributes to several processes in addition to flowering, but is not implicated in all of the phenotypes influenced by GI. Seedlings of Col-0, the cdf1-R cdf2-1 cdf3-1 cdf5-1 quadruple mutant, gi-100 and gi-100 cdf1-R cdf2-1 cdf3-1 cdf5-1 quintuple mutant were grown for 10 days under LD conditions (16h light/8h dark). The aerial part of the seedlings was collected at ZT12 and RNA was prepared from three biological replicas

2015-07-31 | E-GEOD-59996 | biostudies-arrayexpress

Co-administration of MDR1 and BCRP or EGFR/PI3K inhibitors overcomes lenvatinib resistance in hepatocellular carcinoma

Project description:To investigate the mechanism of lenvatinib resistance, we established the lenvatinib resistant Huh7 (Huh7 LR) cells by continuous exposuring to lenvatinib (1–20 μM) for approximately 10 months. We then performed gene expression profiling analysis using data obtained from RNA-seq of Huh7 parental (Huh7 P) cells and the lenvatinib resistant Huh7 (Huh7 LR) cells.

2022-08-26 | GSE211850 | GEO

Identification of genes regulated by GIGANTEA (GI), the CYCLING DOF FACTORS (CDFs) and the GI-CDF module

2015-07-31 | GSE59996 | GEO