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Safety and Efficacy of Anlotinib in Combination With Irinotecan in Patients With Pretreated Advanced Colorectal Cancer

ABSTRACT: Patients with pretreated advanced colorectal cancer are recruited to the phase I portion of this prospective non-randomised study in an escalated dose cohort. The primary endpoint of the dose-escalation phase is to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of anlotinib when given in combination with irinotecan. The phase II (dose-expansion) portion is designed to characterize the safety and potential efficacy of the combination therapy in pretreated advanced colorectal cancer patients.

DISEASE(S): Colorectal Neoplasms,Colo-rectal Cancer

PROVIDER: 2274506 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Role of Anlotinib-induced CCL2 decrease in anti-angiogensis and response prediction for Non-Small Cell Lung Cancer therapy

Project description:Purpose: Our previous clinical trials have been demonstrated that Anlotinib can inhibit tumor growth upon refractory advanced non-small cell lung cancer (NSCLC) patients with the possibility mechanism of anti-angiogenesis. The present study sought to reveal the underlying molecular mechanism of Anlotinib-induced anti-angiogenesis in advanced NSCLC. Experimental Design: Computed tomography (CT) was used to evaluate the treatment effect of Anlotinib upon refractory advanced NSCLC patients. Transcriptome profiling was performed to identify the key gene expression alteration in NCI-H1975 cells before and after Anlotinib treatment. NCI-H1975 derived xenograft model was applied to investigate treatment effect and verify anti-angiogenesis mechanism of Anlotinib. Results: Anlotinib induces tumor cytotoxicity on refractory advanced NSCLC patients, NCI-H1975 derived xenograft models and lung adenocarcinoma cell lines. Transcriptome profiling revealed CCL2 blockade could be responsible for Anlotinib-induced anti-angiogenesis. NCI-H1975 derived xenograft model demonstrated Anlotinib-induced CCL2 blockade play an important role in anti-angiogenesis. Conclusions: This study not only offered the first evidence that Anlotinib inhibits angiogenesis via blocking CCL2 expression, but also provided a novel theoretical basis for the application of Anlotinib in advanced NSCLC patients.

2018-11-30 | E-MTAB-5997 | biostudies-arrayexpress

Transcriptome profiling of Anlotinib-resistant NCI-H1975 and Anlotinib-treated Anlotinib-resistant NCI-H1975

Project description:Further to our previous study (E-MTAB-5997), here we performed transcriptome profiling on Anlotinib-resistant NCI-H1975 and Anlotinib-treated Anlotinib-resistant NCI-H1975, and would like to understand the effects of Anlotinib on Anlotinib-resistant NCI-H1975 cell, compare the different transcriptome profiling on NCI-H1975 cells and Anlotinib-resistant NCI-H1975 cells, sought to find the biomarker for explaining Anlotinib resistance.

2019-07-01 | E-MTAB-7068 | biostudies-arrayexpress

Enhancing Tumor Targeting of Antitumor Drugs through Anlotinib-Mediated Modulation of Extracellular Matrix and RhoA/ROCK Signaling Pathway

Project description:In this study, our research focused on investigating the impact of Anlotinib in enhancing the tumor targeting of antitumor drugs in vivo. Through RNA-sequencing and Label-free quantitative proteomics analysis, we discovered that Anlotinib effectively regulated the expression of extracellular matrix (ECM) genes and proteins, leading to a significant reduction in ECM stiffness. Our bioinformatic analysis indicated a potential positive relationship between the ECM pathways and gefitinib resistance, poor PD-1 treatment outcomes, as well as unfavorable prognosis in lung cancer patients following chemotherapy. To evaluate the efficacy of Anlotinib, we administered it in combination with anti-PD-1/PD-L1 agents, chemotherapeutic drugs, and gefitinib, and visualized their distribution using fluorescent labeling in various tumor types. Notably, our results demonstrated that Anlotinib substantially improved the drug targeting process by prolonging the retention time of antitumor drugs at the tumor site. Moreover, the combination therapy induced a notable loosening of the tumor tissue structure compared to the control group. This reduction in stiffness was further associated with decreased interstitial fluid pressures and tumor solid pressure. Additionally, we observed that Anlotinib effectively suppressed the RhoA/ROCK signaling pathway, inhibiting the formation of stress fibers. These findings strongly suggest that Anlotinib enhances the distribution and retention of antitumor drugs in tumors by modulating ECM expression and physical properties through the RhoA/ROCK signaling pathway. These valuable insights contribute to the development of combination therapies aimed at improving tumor targeting in cancer treatment.

2024-07-31 | GSE237818 | GEO

Transcriptome profiling of Anlotinib-resistant NCI-H1975 and Anlotinib-treated Anlotinib-resistant NCI-H1975

Project description:Transcriptome profiling of Anlotinib-resistant NCI-H1975 and Anlotinib-treated Anlotinib-resistant NCI-H1975

| PRJEB27916 | ENA

Gene expression after human SW982 cells treated with anlotinib by a microarray profiling (Affymetrix)

Project description:Anlotinib could significantly suppresses synovial sarcoma proliferation in PDTX model and cell lines. To identify potential anlotinib targets in synovial sarcoma, we performed a microarray profiling (Affymetrix) in human SW982 cells treated with anlotinib.

2019-01-01 | GSE109468 | GEO

Gene expression after human PANC-1 cells treated with anlotinib by a microarray profiling (Affymetrix)

Project description:Anlotinib exerted cytotoxity on pancreatic cancer cells. To identify potential anlotinib targets in pancreatic cancer, we performed a microarray profiling (Affymetrix) in human PANC-1 cells treated with anlotinib.

2020-12-21 | GSE163574 | GEO

Combination of Eribulin and Anlotinib Exerts Synergistic Cytotoxicity in Retroperitoneal Liposarcoma by Inducing Endoplasmic Reticulum Stress

Project description:Primary retroperitoneal liposarcoma (RLPS) is a rare heterogeneous tumor occurring within retroperitoneal space, and its overall survival did not improve much in the past few decades. Based on a small-sample clinical practice at our center, patients with RLPS can greatly benefit from combination of anlotinib and eribulin. In this study, we investigated combinational effect of anlotinib and eribulin on RLPS. Through transcriptome analysis, we uncovered and validated that synergistic effect mainly induced by endoplasmic reticulum stress (ERS) pathway both in vitro and in vivo.

2024-08-01 | GSE261076 | GEO

Chromatin accessibility analysis uncovers TFAP2A as a regulator on pro-angiogenesis of acquired resistance to anlotinib

Project description:Anlotinib, a multitarget agent a multi-target agent that inhibits tumor proliferation and angiogenesis, has been demonstrated to be effective for non-small cell lung cancer (NSCLC) at third-line or over third-line. However, the underlying mechanisms of anlotinib acquired-resistance is still unclear. Here we performed chromatin accessibility profiling on anlotinib-resistant NCI-H1975 and wild-type NCI-H1975. By integrating with transcriptome analysis, we found that anlotinib resistance was due to increased angiogenic capacity, and revealed that TFAP2A was involved in anlotinib resistance. Next, TFAP2A was knock-down in anlotinib-resistant cells and RNAseq was performed to see down-regulated genes with TFAP2A KD.

2020-11-09 | GSE142031 | GEO

Pancreatic cancer cells treated with anlotinib

Project description:Aberrant regulation of angiogenesis involves in the growth and metastasis of tumors, but angiogenesis inhibitors fail to improve overall survival of pancreatic cancer patients in previous phase III clinical trials. A comprehensive knowledge of the mechanism of angiogenesis inhibitors against pancreatic cancer is helpful for clinical purpose and for the selection of patients who might benefit from the inhibitors. In this work, multi-omics analyses (transcriptomics, proteomics and phosphoproteomics profiling) were carried to delineate the mechanism of anlotinib, a novel angiogenesis inhibitor, against pancreatic cancer cells.

2021-09-09 | PXD023344 | Pride

Anlotinib Combined With mXELIRI as Second-line Treatment of Advanced Colorectal Cancer

Project description:1. Determine the maximum tolerable dose (MTD) and / or phase II recommended dose (RP2D) of the allotinib combined mXELIRI protocol. 2. To evaluate the safety and tolerance of the combination of anlotinib and mXELIRI in the second-line treatment of patients with advanced colorectal cancer

| 2388996 | ecrin-mdr-crc

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