Glioblastoma multiforme (GBM) is known to be the most common and lethal malignant primary brain tumor. Despite vigorous basic and clinical studies over the past decades, the prognosis of patients with GBM has remained dismal. The fundamental problem with these malignancies occurs due to tumor cells' highly infiltrative nature, precluding a complete surgical resection, and a productive or acquired resistance to cytotoxic therapy. Recent studies demonstrated that GBMs exhibited remarkable cellular heterogeneity and hierarchy containing self-renewing glioma stem cells (GSCs). The malignant growth of GBM can be propagated and sustained by GSCs that are endowed with highly efficient clonogenic and tumor initiation capacities. GSCs can be identified with technical support and are responsible for the invasive potential and recurrence of GBMs. They share core signaling pathways with normal neural stem cells, but also display critical distinctions that provide important clues for useful therapeutic targets. Therefore, targeting GSCs becomes priorities for the development of novel therapeutic paradigms. Herein, we reviewed the existing and promising targeting therapies for GSCs which could effectively inhibit the tumor invasion, proliferation and recurrence of GBMs. Significant features of GSCs, such as invasive growth pattern, angiogenic potential, resistance to traditional therapy and differentiation, are important therapeutic targets. More promising strategies should target GSCs themselves by taking advantages of highthroughput technologies and dissecting the intrinsic molecular nature of GSCs. Novel chemical medicines targeting these GSCs may represent one of the most important directions. Hopefully, this could shed a light on the path we are going to.

In this report, we describe the spontaneous malignant transformation of long-term cultured human fetal striatum neural stem cells (hsNSCs, passage 17). After subcutaneous transplantation of long-term cultured hsNSCs into immunodeficient nude mice, 2 out of 15 mice formed xenografts which expressed neuroendocrine tumor markers CgA and NSE. T1 cells, a cell line that we derived from one of the two subcutaneous xenografts, have undergone continuous expansion in vitro. These T1 cells showed stem cell-like features and expressed neural stem cell markers nestin and CD133. The T1 cells were involved in abnormal karyotype, genomic instability and fast proliferation. Importantly, after long-term in vitro culture, the T1 cells did not result in subcutaneous xenografts, but induced intracranial tumor formation, indicating that they adjusted themselves to the intracranial microenvironment. We further found that the T1 cells exhibited an overexpressed level of EGFR, and the CD133 positive T1 cells showed a truncation mutation in the exons 2-7 of the EGFR (EGFRvIII) gene. These results suggest that continuous expansion of neural stem cells in culture may lead to malignant spontaneous transformation. This phenomenon may be functionally related to EGFR by EGFRvIII gene mutation.

Despite the tremendous success of targeted and conventional therapies for lung cancer, therapeutic resistance is a common and major clinical challenge. RNF8 is a ubiquitin E3 ligase that plays essential roles in the DNA damage response; however, its role in the pathogenesis of lung cancer is unclear. Here, we report that RNF8 is overexpressed in lung cancer and positively correlates with the expression of p-Akt and poor survival of patients with non-small-cell lung cancer. In addition, we identify RNF8 as the E3 ligase for regulating the activation of Akt by K63-linked ubiquitination under physiological and genotoxic conditions, which leads to lung cancer cell proliferation and resistance to chemotherapy. Together, our study suggests that RNF8 could be a very promising target in precision medicine for lung cancer.

Lidamycin (LDM, also known as C-1027) as an anti-cancer agent inhibits growth in a variety of cancer cells by inducing apoptosis and cell cycle arrest. In this study we demonstrated that inhibition of mouse embryonic carcinoma (EC) cell growth using LDM at low concentrations can be attributed to a loss of the cell's self-renewal capability but not to apoptosis or cell death, which can be correlated to the down-regulation of embryonic stem (ES) cell-like genes Oct4, Sox2 and c-Myc. MTT assays showed that LDM inhibited the growth of mouse P19 EC cells in a time- and dose-dependent manner. The EC cells exposed to a low dose (0.01 nM) of LDM lost their capability to generate colonies, as evidenced by the colony forming assay. Flow cytometer analyses demonstrated that LDM induced G1 arrest in exposed EC cells without apoptosis. Real-time qPCR, Western blotting and immunocytochemistry revealed that Oct4, Sox2 and c-Myc were down-regulated in LDM-exposed EC cells, but not adriamycin (ADM)-exposed cells. Furthermore, a combination of the low dose of LDM and ADM significantly reduced the proliferation of the cancer cells than single-agent treatment. This suggested that synergy of ADM and LDM improved chemotherapy. Taking together, our results indicate that LDM can reduce the capability for self-renewal that mouse EC cells possess through the repression of ES cell-like genes, thereby inhibiting carcinoma cell growth. This data also suggests that LDM might have potential for application in CSC-based therapy and be a useful tool for studying ES cell pluripotency and differentiation.

These results suggest that LyGDI has significant potential as a marker for detection of ovarian cancer in the patients with ovarian enlargement, including detection of early-stage cancers.