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Your search keyword '"Wongvipat J"' showing total 2 results
Start Over Author "Wongvipat J" Publisher american association for the advancement of science
2 results on '"Wongvipat J"'

1. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer.

Author

Mu P, Zhang Z, Benelli M, Karthaus WR, Hoover E, Chen CC, Wongvipat J, Ku SY, Gao D, Cao Z, Shah N, Adams EJ, Abida W, Watson PA, Prandi D, Huang CH, de Stanchina E, Lowe SW, Ellis L, Beltran H, Rubin MA, Goodrich DW, Demichelis F, and Sawyers CL

Subjects
Benzamides, Cell Line, Tumor, Cell Lineage, Cell Plasticity, Humans, Male, Nitriles, Phenylthiohydantoin therapeutic use, Prostatic Neoplasms genetics, SOXB1 Transcription Factors genetics, Androgen Antagonists therapeutic use, Phenylthiohydantoin analogs & derivatives, Prostatic Neoplasms drug therapy, Prostatic Neoplasms pathology, Retinoblastoma Binding Proteins genetics, SOXB1 Transcription Factors metabolism, Tumor Suppressor Protein p53 genetics, Ubiquitin-Protein Ligases genetics
Abstract

Some cancers evade targeted therapies through a mechanism known as lineage plasticity, whereby tumor cells acquire phenotypic characteristics of a cell lineage whose survival no longer depends on the drug target. We use in vitro and in vivo human prostate cancer models to show that these tumors can develop resistance to the antiandrogen drug enzalutamide by a phenotypic shift from androgen receptor (AR)-dependent luminal epithelial cells to AR-independent basal-like cells. This lineage plasticity is enabled by the loss of TP53 and RB1 function, is mediated by increased expression of the reprogramming transcription factor SOX2, and can be reversed by restoring TP53 and RB1 function or by inhibiting SOX2 expression. Thus, mutations in tumor suppressor genes can create a state of increased cellular plasticity that, when challenged with antiandrogen therapy, promotes resistance through lineage switching., (Copyright © 2017, American Association for the Advancement of Science.)

Published
2017
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2. Development of a second-generation antiandrogen for treatment of advanced prostate cancer.

Author

Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, Wongvipat J, Smith-Jones PM, Yoo D, Kwon A, Wasielewska T, Welsbie D, Chen CD, Higano CS, Beer TM, Hung DT, Scher HI, Jung ME, and Sawyers CL

Subjects
Androgen Antagonists metabolism, Androgen Antagonists pharmacokinetics, Androgen Antagonists pharmacology, Anilides metabolism, Anilides pharmacology, Animals, Antineoplastic Agents metabolism, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents pharmacology, Benzamides, Biological Availability, Cell Line, Tumor, Cell Nucleus metabolism, Cell Proliferation drug effects, DNA metabolism, Drug Screening Assays, Antitumor, Gene Expression Regulation, Neoplastic drug effects, Humans, Male, Mice, Nitriles metabolism, Nitriles pharmacology, Phenylthiohydantoin metabolism, Phenylthiohydantoin pharmacokinetics, Phenylthiohydantoin pharmacology, Phenylthiohydantoin therapeutic use, Prostatic Neoplasms pathology, Receptors, Androgen chemistry, Receptors, Androgen genetics, Receptors, Androgen metabolism, Tosyl Compounds metabolism, Tosyl Compounds pharmacology, Transcription, Genetic drug effects, Xenograft Model Antitumor Assays, Androgen Antagonists therapeutic use, Antineoplastic Agents therapeutic use, Phenylthiohydantoin analogs & derivatives, Prostatic Neoplasms drug therapy
Abstract

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. RD162 and MDV3100 are orally available and induce tumor regression in mouse models of castration-resistant human prostate cancer. Of the first 30 patients treated with MDV3100 in a Phase I/II clinical trial, 13 of 30 (43%) showed sustained declines (by >50%) in serum concentrations of prostate-specific antigen, a biomarker of prostate cancer. These compounds thus appear to be promising candidates for treatment of advanced prostate cancer.

Published
2009
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