Publications by authors named "David T Hung"

Although new targeted therapies, such as ibrutinib and idelalisib, have made a large impact on non-Hodgkin's lymphoma (NHL) patients, the disease is often fatal because patients are initially resistant to these targeted therapies, or because they eventually develop resistance. New drugs and treatments are necessary for these patients. One attractive approach is to inhibit multiple parallel pathways that drive the growth of these hematologic tumors, possibly prolonging the duration of the response and reducing resistance.

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Article Synopsis
  • Aberrant B-cell activation is linked to various cancers and blood disorders, making them a target for treatment.
  • BTK and PI3Kδ are important kinases involved in B-cell signaling, and their inhibitors have shown promise in treating specific lymphomas.
  • The study introduces new compounds that effectively inhibit both BTK and PI3Kδ, potentially enhancing treatment responses and addressing resistance in B-cell diseases.
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  • EZH2 is a crucial component of the PRC2 complex, responsible for adding methyl groups to histone H3, which can influence gene expression and is linked to various cancers when dysregulated.
  • Developing EZH2 inhibitors has become a key focus in cancer therapy, with many existing inhibitors featuring a bicyclic heteroaryl structure.
  • This study presents the creation of new EZH2 inhibitors based on an indoline core, which show strong effectiveness (nanomolar activity) while enhancing solubility and stability against oxidative breakdown.
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While enzalutamide and abiraterone are approved for treatment of metastatic castration-resistant prostate cancer (mCRPC), approximately 20-40% of patients have no response to these agents. It has been stipulated that the lack of response and the development of secondary resistance to these drugs may be due to the presence of AR splice variants. HDAC6 has a role in regulating the androgen receptor (AR) by modulating heat shock protein 90 (Hsp90) acetylation, which controls the nuclear localization and activation of the AR in androgen-dependent and independent scenarios.

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Temozolomide is a chemotherapeutic agent that is used in the treatment of glioblastoma and other malignant gliomas. It acts through DNA alkylation, but treatment is limited by its systemic toxicity and neutralization of DNA alkylation by upregulation of the O-methylguanine-DNA methyltransferase gene. Both of these limiting factors can be addressed by achieving higher concentrations of TMZ in the brain.

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Metastatic prostate cancer is treated with drugs that antagonize androgen action, but most patients progress to a more aggressive form of the disease called castration-resistant prostate cancer, driven by elevated expression of the androgen receptor. Here we characterize the diarylthiohydantoins RD162 and MDV3100, two compounds optimized from a screen for nonsteroidal antiandrogens that retain activity in the setting of increased androgen receptor expression. Both compounds bind to the androgen receptor with greater relative affinity than the clinically used antiandrogen bicalutamide, reduce the efficiency of its nuclear translocation, and impair both DNA binding to androgen response elements and recruitment of coactivators.

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