Browsing by Author "Liang, Chaozhao"

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    Targeting androgen receptor-independent pathways in therapy-resistant prostate cancer.
    (Asian journal of urology, 2019-01) Xu, Lingfan; Chen, Junyi; Liu, Weipeng; Liang, Chaozhao; Hu, Hailiang; Huang, Jiaoti
    Since androgen receptor (AR) signaling is critically required for the development of prostate cancer (PCa), targeting AR axis has been the standard treatment of choice for advanced and metastatic PCa. Unfortunately, although the tumor initially responds to the therapy, treatment resistance eventually develops and the disease will progress. It is therefore imperative to identify the mechanisms of therapeutic resistance and novel molecular targets that are independent of AR signaling. Recent advances in pathology, molecular biology, genetics and genomics research have revealed novel AR-independent pathways that contribute to PCa carcinogenesis and progression. They include neuroendocrine differentiation, cell metabolism, DNA damage repair pathways and immune-mediated mechanisms. The development of novel agents targeting the non-AR mechanisms holds great promise to treat PCa that does not respond to AR-targeted therapies.
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    Therapeutic potential of ReACp53 targeting mutant p53 protein in CRPC.
    (Prostate cancer and prostatic diseases, 2020-03) Zhang, Yaqun; Xu, Lingfan; Chang, Yan; Li, YanJing; Butler, William; Jin, Er; Wang, Aifen; Tao, Yulei; Chen, Xufeng; Liang, Chaozhao; Huang, Jiaoti
    BACKGROUNDS:p53 is a tumor suppressor that prevents cancer onset and progression, and mutations in the p53 gene cause loss of the tumor suppressor function of the protein. The mutant p53 protein in tumor cells can form aggregates which contribute to the dominant-negative effect over the wild-type p53 protein, causing loss of p53 tumor suppression or gain of novel oncogenic functions. Mutations in p53 have been implicated in the pathogenesis of primary prostate cancer (PCa), and are often detected in recurrent and metastatic disease. Thus, targeting mutant p53 may constitute an alternative therapeutic strategy for advanced PCa for which there are no other viable options. METHODS:In this study, we used immunoprecipitation, immunofluorescence, clonogenic survival, and cell proliferation assays, flow cytometric analysis and in vivo xenograft to investigate the biological effects of ReACp53, a cell-permeable peptide inhibitor of p53 aggregation, on mutant p53-carrying PCa cells. RESULTS:Our results show that ReACp53 targets amyloid aggregates of mutant p53 protein and restores the p53 nuclear function as transcriptional factor, induces mitochondrial cell death and reduces DNA synthesis of mutant p53-carrying PCa cells; ReACp53 also inhibits xenograft tumor growth in vivo. CONCLUSIONS:The data presented here suggest a therapeutic potential of targeting mutant p53 protein in advanced PCa setting, which has a clinical impact for aggressive PCa with transforming how such tumors are managed.