Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO ...
Microtubule-targeting agents are an important class of anti-cancer drugs; their full potential is however not realized because of significant myelotoxicity and neurotoxicity. We here report 3-nitropyridine analogues as a novel group of microtubule-targeting agents with potent anti-cancer effects against a broad range of cancer types. We show that t...
Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membran...
Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies a...
Three 2D heterospin radical-3d–4f networks with the formula {[Ln(hfac)3]2[M(hfac)2](NIT-3Py-5-Pyoe)2}n (MII = CoII and LnIII = Gd 1, Dy 2; MII = CuII and LnIII = Dy 3; NIT-3Py-5-Pyoe = (2-(5-(4-pyridinone)-3-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide)) have been successfully constructed using a novel multidentate nitronyl nitroxide para...
EWS fusion oncoproteins underlie several human malignancies including Desmoplastic Small Round Cell Tumor (DSRCT), an aggressive cancer driven by EWS-WT1 fusion proteins. Here we combine chromatin occupancy and 3D profiles to identify EWS-WT1-dependent gene regulation networks and target genes. We show that EWS-WT1 is a powerful chromatin activator...
Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma. For the alveolar subtype (ARMS), the presence of the PAX3::FOXO1 fusion gene and/or metastases are strong predictors of poor outcome. Metastatic PAX3::FOXO1+ ARMS often responds to chemotherapies initially, only to subsequently relapse and become resistant with most patients f...
BackgroundMost patients with metastatic gastroesophageal adenocarcinoma (mGEA) progress on immune checkpoint inhibitors (ICIs). Novel approaches to overcome resistance to ICI in mGEA are needed. Cabozantinib is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI. This study evaluated the combination of cabozanti...
Published in Angewandte Chemie (International ed. in English)
Acremolactone B is a pyridine-containing azaphilone-type polyketide. The first total synthesis of this molecule was achieved on a gram scale, based on an aza-6π electrocyclization-aromatization strategy for construction of the tetra-substituted pyridine ring. A bicyclic intermediate was expeditiously prepared by using [2+2] photocycloaddition and c...
Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have revolutionized breast cancer therapy. However,
