Background: Bladder cancer is commonly diagnosed in patients ineligible for radical cystectomy or chemoradiotherapy (chemo-RT) with cisplatin or fluorouracil with mitomycin. We assessed tolerability, efficacy, and toxicity of hypofractionated radiotherapy with...
PUBLICATIONS
Clinical Activity of Olaparib in Urothelial Bladder Cancer With DNA Damage Response Gene Mutations
No abstract available Authors: Randy F Sweis 1, Brian Heiss 1, Jeremy Segal 1, Lauren Ritterhouse 1, Sabah Kadri 1, Jane E Churpek 1, Kenisha Allen 1, Dawn Conway 1, Carolyn Marinier, Norm D Smith 1, Sean P Pitroda 1, Walter M Stadler
Optimization of Preclinical Metabolism for Somatostatin Receptor Subtype 5-Selective Antagonists
A series of structurally diverse azaspirodecanone and spirooxazolidinone analogues were designed and synthesized as potent and selective somatostatin receptor subtype 5 (SSTR5) antagonists. Four optimized compounds each representing a subseries showed improvement in...
T Cell-Inflamed versus Non-T Cell-Inflamed Tumors: A Conceptual Framework for Cancer Immunotherapy Drug Development and Combination Therapy Selection
Immunotherapies such as checkpoint-blocking antibodies and adoptive cell transfer are emerging as treatments for a growing number of cancers. Despite clinical activity of immunotherapies across a range of cancer types, the majority of patients fail to respond to these...
Low clinical adoption of tumor genomic profiling: cause for concern?
No abstract available Authors: Michael W Drazer, Randy F Sweis
Pseudoprogression manifesting as recurrent ascites with anti-PD-1 immunotherapy in urothelial bladder cancer
Case Reports Background: Immunotherapies targeting the PD-1 checkpoint pathway have recently gained regulatory approval in numerous cancer types. With the widespread use of immune checkpoint therapies, varying patterns of responses and immune-related adverse events...
SAR and characterization of non-substrate isoindoline urea inhibitors of nicotinamide phosphoribosyltransferase (NAMPT)
Herein we disclose SAR studies that led to a series of isoindoline ureas which we recently reported were first-in-class, non-substrate nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. Modification of the isoindoline and/or the terminal functionality of...
Erratum: The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex
Published Erratum No abstract available Authors: Yupeng He, Sujatha Selvaraju, Michael L Curtin, Clarissa G Jakob, Haizhong Zhu, Kenneth M Comess, Bailin Shaw, Juliana The, Evelyne Lima-Fernandes, Magdalena M Szewczyk, Dong Cheng, Kelly L Klinge, Huan-Qiu Li, Marina...
Mechanistic and pharmacologic insights on immune checkpoint inhibitors
Review The concept of augmenting the immune system to eradicate cancer dates back at least a century. A major resurgence in cancer immunotherapy has occurred over the past decade since the identification and targeting of negative regulators with antibody therapies to...
The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex
Polycomb repressive complex 2 (PRC2) is a regulator of epigenetic states required for development and homeostasis. PRC2 trimethylates histone H3 at lysine 27 (H3K27me3), which leads to gene silencing, and is dysregulated in many cancers. The embryonic ectoderm...