RESUMO
Prostate cancer (PCa) is a highly heterogeneous disease and typically presents with multiple distinct cancer foci. Heterogeneity in androgen receptor (AR) expression levels in PCa has been observed for decades, from untreated tumors to castration-resistant prostate cancer (CRPC) to disseminated metastases. Current standard-of-care therapies for metastatic CRPC can only extend life by a few months. Cancer stem cells (CSCs) are defined as a subpopulation of cancer cells that exists in almost all treatment-naive tumors. Additionally, non-CSCs may undergo cellular plasticity to be reprogrammed to prostate cancer stem cells (PCSCs) during spontaneous tumor progression or upon therapeutic treatments. Consequently, PCSCs may become the predominant population in treatment-resistant tumors, and the "root cause" for drug resistance. microRNA-34a (miR-34a) is a bona fide tumor-suppressive miRNA, and its expression is dysregulated in PCa. Importantly, miR-34a functions as a potent CSC suppressor by targeting many molecules essential for CSC survival and functions, which makes it a promising anti-PCSC therapeutic. Here, we conducted a comprehensive literature survey of miR-34a in the context of PCa and especially PCSCs. We provided an updated overview on the mechanisms of miR-34a regulation followed by discussing its tumor suppressive functions in PCa. Finally, based on current advances in miR-34a preclinical studies in PCa, we offered potential delivery strategies for miR-34a-based therapeutics for treating advanced PCa.
RESUMO
Like BRCA2, MAGEC3 is an ovarian cancer predisposition gene that has been shown to have prognostic significance in ovarian cancer patients. Despite the clinical significance of each gene, no studies have been conducted to assess the clinical significance of their combined expression. We therefore sought to determine the relationship between MAGEC3 and BRCA2 expression in ovarian cancer and their association with patient characteristics and outcomes. Immunohistochemical staining was quantitated on tumor microarrays of human tumor samples obtained from 357 patients with epithelial ovarian cancer to ascertain BRCA2 expression levels. In conjunction with our previously published MAGEC3 expression data, we observed a weak inverse correlation of MAGEC3 with BRCA2 expression (r = −0.15; p < 0.05) in cases with full-length BRCA2. Patients with optimal cytoreduction, loss of MAGEC3, and detectable BRCA2 expression had better overall (median OS: 127.9 vs. 65.3 months, p = 0.035) and progression-free (median PFS: 85.3 vs. 18.8 months, p = 0.002) survival compared to patients that were BRCA2 expressors with MAGEC3 normal levels. Our results suggest that combined expression of MAGEC3 and BRCA2 serves as a better predictor of prognosis than each marker alone.