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Molecular Cancer Therapeutics
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#1Francesca Trotta (University of Calabria)H-Index: 2
#2Paola Avena (University of Calabria)H-Index: 13
Last. Catia Pilon (UNIPD: University of Padua)H-Index: 20
view all 18 authors...
Mitotane causes hypercholesterolemia in ACC patients. We suppose that cholesterol increases within the tumor and can be used to activate proliferative pathways. In this study, we used statins to decrease intratumor cholesterol and investigated the effects on ACC growth related to ERα action at the nuclear and mitochondrial levels. We first used microarray to investigate mitotane effect on genes involved in cholesterol homeostasis and evaluated their relationship with patients' survival in ACC TC...
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Glucocorticoids are widely used for therapy of hematological malignancies. Unfortunately, chronic treatment with glucocorticoids commonly leads to adverse effects including skin and muscle atrophy and osteoporosis. We found recently that REDD1 (regulated in development and DNA damage 1) plays central role in steroid atrophy. Here we tested whether REDD1 suppression makes glucocorticoid-based therapy of blood cancer safer. Unexpectedly, ~50% of top putative REDD1 inhibitors selected by bioinforma...
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#1Patrick J. RobertsH-Index: 15
#2Vishnu Kumarasamy (Roswell Park Cancer Institute)H-Index: 3
Last. Erik S. Knudsen (Roswell Park Cancer Institute)H-Index: 21
view all 4 authors...
Cyclin-dependent kinases 4 and 6 (CDK4/6) have emerged as important therapeutic targets. Pharmacological inhibitors of these kinases function to inhibit cell cycle progression and exert other important effects on the tumor and host environment. Due to their impact on the cell cycle, CDK4/6 inhibitors (CDK4/6i) have been hypothesized to antagonize the anti-tumor effects of cytotoxic chemotherapy in tumors that are CDK4/6 dependent. However, there are multiple preclinical studies that illustrate p...
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#1Bettina Brauchle (LMU: Ludwig Maximilian University of Munich)H-Index: 1
#2Rebecca Goldstein (Amgen)H-Index: 2
Last. Sascha Haubner (LMU: Ludwig Maximilian University of Munich)H-Index: 6
view all 26 authors...
Despite advances in the treatment of acute myeloid leukemia (AML), novel therapies are needed to induce deeper and more durable clinical response. Bispecific T cell Engager (BiTE®) molecules, which redirect patient T cells to lyse tumor cells, are a clinically-validated modality for hematologic malignancies. Due to broad AML expression and limited normal tissue expression, FLT3 is proposed to be an optimal BiTE® molecule target. Expression profiling of FLT3 was performed in primary AML patient s...
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#1Joshua M. Abbott (CU: University of Colorado Boulder)H-Index: 1
#2Qiong Zhou (CU: University of Colorado Boulder)H-Index: 10
Last. Todd M. Pitts (Anschutz Medical Campus)H-Index: 22
view all 15 authors...
Since the discovery of CHD1L in 2008 it has emerged as an oncogene implicated in the pathology and poor prognosis of a variety of cancers, including gastrointestinal cancers. However, a mechanistic understanding of CHD1L as a driver of colorectal cancer (CRC) has been limited. Until now, there have been no reported inhibitors of CHD1L, also limiting its development as a molecular target. We sought to characterize the clinicopathological link between CHD1L and CRC, determine the mechanism(s) by w...
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Last. Ling Huang (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 5
view all 15 authors...
Metastasis development is the leading cause of cancer-related mortality in pancreatic ductal adenocarcinoma (PDAC) and yet, few preclinical systems to recapitulate its full spreading process are available. Thus, modeling of tumor progression to metastasis is urgently needed. In this work, we describe the generation of highly metastatic PDAC patient-derived xenograft (PDX) mouse models and subsequent single-cell RNA sequencing of circulating tumor cells (CTC), isolated by human HLA sorting, to id...
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Conventional antibody drug conjugates (ADC) utilize native surface-exposed lysines or cysteines on the antibody of interest to conjugate cytotoxic payload. The non-specific conjugation results in a mixture with variable drug-to-antibody ratios (DARs), conjugation sites, and ADCs that are often unstable in systemic circulation. ARX788 is an ADC consisting of a HER2-targeting antibody site-specifically conjugated with a potent anti-tubulin cytotoxic drug-linker, AS269. The site-specific conjugatio...
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Most osteosarcoma (OS) patients have subclinical pulmonary micrometastases at diagnosis. Mounting evidence suggests that macrophages facilitate metastasis. As the epidermal growth factor receptor (EGFR) has been implicated in carcinoma-macrophage crosstalk, in this study we asked whether gefitinib, an EGFR inhibitor, reduces OS invasion and metastatic outgrowth using the K7M2-Balb/c syngeneic murine model. Macrophages enhanced OS invasion in vitro, which was suppressed by gefitinib. Oral gefitin...
1 CitationsSource
#1Ling Zeng (UAB: University of Alabama at Birmingham)H-Index: 2
#2Anatoly Nikolaev (UAB: University of Alabama at Birmingham)H-Index: 1
Last. Eddy S. Yang (UAB: University of Alabama at Birmingham)H-Index: 29
view all 5 authors...
Platinum-based chemoradiotherapy is a mainstay of organ-preserving therapy for head and neck squamous cell carcinoma cancer (HNSCC) patients. However, the disease eventually becomes resistant to treatment necessitating new therapies. Checkpoint kinase 1 and 2 (CHK1/2) are serine/threonine kinases that activate cell cycle checkpoints and serve a critical role in the DNA-damage response (DDR). As resistance to cisplatin and radiation may involve a heightened DDR, we hypothesized that prexasertib, ...
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#1Ying Xu (Sichuan University)H-Index: 5
#2Qianqian Wang (Sichuan University)H-Index: 2
Last. Weiqiong Zuo (Sichuan University)H-Index: 7
view all 13 authors...
Castration-resistant prostate cancer (CRPC) is a lethal disease with few treatment alternatives once patients become resistant to second-generation anti-androgens. In CRPC, BET proteins are key regulators of AR- and MYC-mediated transcription, while the PLK1 inhibitor potentially downregulates AR and MYC besides influencing the cell cycle. Therefore, synchronous inhibition of BET and PLK1 would be a promising approach for CRPC therapy. This study developed a dual BET and PLK1 inhibitor WNY0824 w...
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Cancer
Molecular biology
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Cancer cell