Inflammation and Androgen Receptor in Prostate Cancer
Dr. Huang's lab studies ties between aberrant activation of androgen receptor and prostate cancer progression and resistance to therapy.
Androgens and androgen receptor play a pivotal role in prostate cancer development, and androgen deprivation therapy is the standard treatment for metastatic prostate cancer. However, the majority of prostate cancers relapse after androgen ablation. Intriguingly, androgen receptor remains functionally active even in the presence of very low levels of androgens.
Inflammation is a protective reaction to infection or cellular injury or damage, but it also has a pathogenic role in many diseases, including cancer. Inflammation appears to be a crucial etiological factor of prostate cancer.
Findings in the literature suggest that the signaling pathways mediating the activation of proinflammatory factor NFB are attractive targets for chemoprevention and chemotherapy for prostate cancer. Indeed, rationalized chemoprevention trials using anti-inflammation drugs have been conducted by others. However, outcomes have been mixed, stressing an urgent need to elucidate the precise role of inflammation in prostate cancer.
Studies in Dr. Huang's lab show that proinflammatory cytokines such as TNFα promote activation of kinase IKKβ, which not only activates NFκB signaling, but also induces β-TRCP-dependent ubiquitination and degradation of androgen receptor, a major promoter of prostate cancer. However, further studies in Dr. Huang's lab show that a few components in this signaling cascade are often deleted or deregulated in patient samples and that deregulation causes elevation of androgen receptor protein, thereby favoring disease progression.
Ongoing research in Dr. Huang's lab aims to understand how inflammation influences androgen receptor signaling and prostate cancer progression. The project is supported by an R01 grant from the National Cancer Institute.