GSE131358 A potent and selective small-molecule degrader of STAT3 achieves complete tumor regression in vivo

We report herein the discovery of SD-36, a small-molecule degrader of STAT3. SD-36 potently induces the degradation of STAT3 protein in vitro and in vivo and demonstrates high selectivity over other STAT members. Induced degradation of STAT3 results in a strong suppression of its transcription network in leukemia and lymphoma cells. SD-36 inhibits the growth of a subset of acute myeloid leukemia and anaplastic large cell lymphoma cell lines by inducing cell cycle arrest and/or apoptosis. SD-36 achieves complete and long-lasting tumor regression in multiple xenograft mouse models at well tolerated dose schedules. Degradation of STAT3 protein therefore represents a promising cancer therapeutic strategy.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

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Keserű Richard Moriggl Signal transducer and activator of transcription (STAT)3 and STAT5 are important transcription factors that are able to mediate or even drive cancer progression through hyperactivation or gain-of-function mutations. Mutated STAT3 is mainly associated with large granular lymphocytic T-cell leukemia, whereas mutated STAT5B is associated with T-cell prolymphocytic leukemia, T-cell acute lymphoblastic leukemia and γδ T-cell-derived lymphomas. Hyperactive STAT3 and STAT5 are also implicated in various hematopoietic and solid malignancies, such as chronic and acute myeloid leukem...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Publication date: Available online 22 November 2019Source: Journal of Geriatric OncologyAuthor(s): Reena Jayani, Ashley Rosko, Rebecca Olin, Andrew ArtzAbstractHematopoietic cell transplant (HCT) is an important aspect of treatment for many hematologic malignancies. As cancer is a disease associated with aging, and hematologic malignancies are no exception, rates of autologous and allogeneic HCT utilization in older adults are on the rise. The most common indications for autologous HCT are multiple myeloma and lymphoma, and for allogenic HCT are acute myeloid leukemia and myelodysplastic syndrome. Older adults into their e...
Source: Journal of Geriatric Oncology - Category: Cancer & Oncology Source Type: research
ConclusionWe suggest a one ‐compartment population model with first‐order elimination to capture the pharmacokinetic profile for basiliximab for this patient population.
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research
Yicheng Ni Cancer remains a major cause of death globally. Given its relapsing and fatal features, curing cancer seems to be something hardly possible for the majority of patients. In view of the development in cancer therapies, this article summarizes currently available cancer therapeutics and cure potential by cancer type and stage at diagnosis, based on literature and database reviews. Currently common cancer therapeutics include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, treatment with curative intent by these methods are mainly eligible for patients with localized diseas...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Publication date: 11 November 2019Source: Cancer Cell, Volume 36, Issue 5Author(s): Longchuan Bai, Haibin Zhou, Renqi Xu, Yujun Zhao, Krishnapriya Chinnaswamy, Donna McEachern, Jianyong Chen, Chao-Yie Yang, Zhaomin Liu, Mi Wang, Liu Liu, Hui Jiang, Bo Wen, Praveen Kumar, Jennifer L. Meagher, Duxin Sun, Jeanne A. Stuckey, Shaomeng WangSummarySignal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Here we report the discovery of SD-36, a small-molecule degrader of STAT3. SD-36 potently induces the degradation of STAT3 protein in vitro and in vivo and demonstrates high ...
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research
s Pabst Amplification and overexpression of the myeloid cell leukemia differentiation protein MCL1 and the murine double minute protein MDM2 have been reported in various human tumors as well as hematological malignancies including acute myeloid leukemia (AML). While MCL1 is an anti-apoptotic member of the BCL-2 family proteins, MDM2 is an important cellular inhibitor of the p53 tumor suppressor. The key oncogene in AML is the FLT3 growth factor receptor gene. FLT3 signaling pathways including the MAPK cascade (RAS-RAF-MEK-ERK) are highly active in AML cells, leading to induced protein translation and cell proliferatio...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Kim De Veirman AXL belongs to the TAM (TYRO3, AXL, and MERTK) receptor family, a unique subfamily of the receptor tyrosine kinases. Their common ligand is growth arrest-specific protein 6 (GAS6). The GAS6/TAM signaling pathway regulates many important cell processes and plays an essential role in immunity, hemostasis, and erythropoiesis. In cancer, AXL overexpression and activation has been associated with cell proliferation, chemotherapy resistance, tumor angiogenesis, invasion, and metastasis; and has been correlated with a poor prognosis. In hematological malignancies, the expression and function of AXL is highly...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Purpose of review With the introduction of new targeted therapies for hematological malignancies comes the challenges of both assessing the risk of developing an IFD while being treated with these agents, as well as managing the drug--drug interactions between azole antifungals and the agents. Recent findings New targeted therapies for hematological malignancy include chimeric antigen receptor T cells (CAR T cells), Bi-specific T-cell Engager (BiTE) blinatumomab, and the antibody–drug conjugate (ADC) of calicheamicin inotuzumab ozogamicin for acute lymphoblasic leukemia (ALL) and lymphoma; the Bruton's tyrosine ...
Source: Current Opinion in Infectious Diseases - Category: Infectious Diseases Tags: ANTIMICROBIAL AGENTS: BACTERIAL/FUNGAL: Edited by Monica Slavin Source Type: research
CONCLUSION: All tested biosimilars demonstrated similar effectiveness and safety profiles in patients with hematological tumors undergoing PBSC mobilization; therefore, they can be used interchangeably. PMID: 31663634 [PubMed - as supplied by publisher]
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: J Clin Apher Source Type: research
This study aimed to characterize the expression pattern of SALL4 gene in adult patients with acute myeloid leukemia. Quantitative Real-time PCR was used to determine the expression level of the gene in peripheral blood of 52 Egyptian adult AML patients and 10 healthy control cases. Our study was done in the National Cancer Institute during the period of time between December 2014 and June 2015. RESULTS: The observed data revealed that none of the studied controls expressed SALL4> 1.0 RQ and there was a highly statistically significant difference between cases and controls regarding SALL4 gene expression where all ca...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
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