Molecular Cancer Therapeutics
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#1Krista M. Dalton (VCU: Virginia Commonwealth University)
#2Kateryna Krytska (Children's Hospital of Philadelphia)H-Index: 9
Last. Anthony C. Faber (VCU: Virginia Commonwealth University)H-Index: 28
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Venetoclax is a small molecule inhibitor of the pro-survival protein BCL-2 that has gained market approval in BCL-2 dependent hematological cancers including chronic lymphocytic leukemia and acute myeloid leukemia. Neuroblastoma (NB) is a heterogenous pediatric cancer with a five-year survival rate of less than 50% for high-risk patients, which include nearly all cases with amplified MYCN. We previously demonstrated that venetoclax is active in MYCN-amplified NB but has limited single-agent acti...
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#1Tomohiro Fujiwara (Okayama University)H-Index: 16
#2Mohamed A. Yakoub (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
Last. John H. Healey (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 96
view all 17 authors...
Colony-stimulating factor 1 (CSF-1) is a primary regulator of the survival, proliferation, and differentiation of monocyte/macrophage that sustains the pro-tumorigenic functions of tumor-associated macrophages (TAMs). Considering current advances in understanding the role of the inflammatory tumor microenvironment, targeting the components of the sarcoma microenvironment, such as TAMs, is a viable strategy. Here, we investigated the effect of PLX3397 (pexidartinib) as a potent inhibitor of the C...
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#1Deborah R. Surman (BCM: Baylor College of Medicine)H-Index: 4
#2Yuan XuH-Index: 22
Last. Robert T. Ripley (BCM: Baylor College of Medicine)H-Index: 1
view all 13 authors...
Approximately 20,000 patients per year are diagnosed with esophageal adenocarcinoma (EAC) and malignant pleural mesothelioma (MPM); fewer than 20% survive five years. Effective therapeutic strategies are limited even though patients receive a combination of chemotherapeutics. These tumors harbor thousands of mutations that contribute to tumor development. Downstream of oncogenic driving mutations, altered tumor mitochondria promote resistance to apoptosis. Dynamic Bcl-2 homology-3 profiling (DBP...
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#1Roger SmithH-Index: 78
#2David J. ZammitH-Index: 3
Last. Sandeep GuptaH-Index: 3
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The 5T4 oncofetal antigen (trophoblast glycoprotein) is expressed in a wide range of malignant tumors but shows very limited expression in normal adult tissues. ASN004 is a 5T4-targeted antibody drug conjugate (ADC) that incorporates a novel single-chain scFv-Fc antibody and Dolaflexin drug-linker technology, with an Auristatin F Hydroxypropylamide payload drug-to-antibody ratio of ca. 10-12. The pharmacology, toxicology and pharmacokinetic properties of ASN004 and its components were investigat...
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#1Hiroshi Ureshino (Saga University)H-Index: 7
#2Yuki Kurahashi (Saga University)H-Index: 1
Last. Shinya Kimura (Saga University)H-Index: 48
view all 16 authors...
DNA methyltransferase inhibitors have improved the prognosis of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, because these agents are easily degraded by cytidine deaminase (CDA), they must be administered intravenously or subcutaneously. Recently, two orally bioavailable DNA methyltransferase inhibitors, CC-486 and ASTX727, were approved. In previous work, we developed 5-O-trialkylsilylated decitabines that resist degradation by CDA. However, the effects of silylatio...
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#1Mark D. Pegram (Stanford University)H-Index: 65
#2Erika Hamilton (Sarah Cannon Research Institute)H-Index: 25
Last. Manish R. Patel (Sarah Cannon Research Institute)H-Index: 32
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MEDI4276 is a biparatopic tetravalent antibody targeting 2 nonoverlapping epitopes in subdomains 2 and 4 of the HER2 ecto-domain, with site-specific conjugation to a tubulysin-based microtubule inhibitor payload. MEDI4276 demonstrates enhanced cellular internalization and cytolysis of HER2+ tumor cells in vitro. This was a first-in-human, dose-escalation clinical trial in patients with HER2+ advanced or metastatic breast cancer (BC) or gastric cancer. MEDI4276 doses escalated from 0.05-0.9 mg/kg...
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#1Shuo Miao (Qingdao University)
#2Qingsong Zhang (Qingdao University)
Last. Jianxun Wang (Qingdao University)H-Index: 26
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In view of the increasing number of malignant tumors worldwide and their high mortality, efforts are being made to find effective biomarkers for early detection and effective treatment measures of cancer. In recent years, the roles of platelets in tumors have attracted considerable attention. Although platelets do not have nuclei, they are rich in microRNAs, which are important molecules in platelet regulation of tumors. Platelet microRNA expression in tumor patients is abnormal and tumor-specif...
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#1Michael P. Sanderson (Merck KGaA)H-Index: 2
#2Manja Friese-Hamim (Merck KGaA)H-Index: 5
Last. Christina Esdar (Merck KGaA)H-Index: 11
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Large multifunctional peptidase 7 (LMP7/β5i/PSMB8) is a proteolytic subunit of the immunoproteasome, which is predominantly expressed in normal and malignant hematolymphoid cells, including multiple myeloma (MM), and contributes to the degradation of ubiquitinated proteins. Described herein for the first time is the preclinical profile of M3258; an orally-bioavailable, potent, reversible and highly-selective LMP7 inhibitor. M3258 demonstrated strong antitumor efficacy in MM xenograft models, inc...
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#1Tomoyoshi Inoue (UCSF: University of California, San Francisco)
#2Thomas Byrne (UCSF: University of California, San Francisco)
Last. Donald M. McDonald (UCSF: University of California, San Francisco)H-Index: 123
view all 14 authors...
Oncolytic vaccinia viruses have promising efficacy and safety profiles in cancer therapy. While antitumor activity can be increased by manipulating viral genes, the relative efficacy of individual modifications has been difficult to assess without side-by-side comparisons. The present study sought to compare the initial antitumor activity after intravenous administration of five vaccinia virus variants of the same Western Reserve backbone and thymidine kinase gene deletion in RIP-Tag2 transgenic...
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#1Danlin Sun (Jiangsu University)
#2Anna S. Nikonova (Fox Chase Cancer Center)H-Index: 15
Last. Erica A. Golemis (Fox Chase Cancer Center)H-Index: 72
view all 14 authors...
Targeted, catalytic degradation of oncoproteins using heterobifunctional small molecules is an attractive modality, particularly for hematological malignancies which are often initiated by aberrant transcription factors and are challenging to drug with inhibitors. BRD4, a member of the Bromodomain and Extraterminal (BET) family, is a core transcriptional and epigenetic regulator that recruits the P-TEFb complex, which includes Cdk9 and cyclin T, to RNA polymerase II (pol II). Together, BRD4 and ...
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