Molecular Approach to Neuroblastoma

Neuroblastoma is a notably malignant cancer originates from neuroblastoma stem cells during embryogenesis. It can originate from any region of the peripheral nervous system. Neuroblastoma is a heterogeneous cancer. The cells responsible for heterogeneous structure are neuroblastoma stem cells that initiate the cancer and generate into all the cancer cells and have self‐renewal property. Although some specific surface markers and genetic patterns of neuroblastoma stem cell were determined, all mechanisms have not been illuminated yet. Mutations that are specific to neuroblastoma development, risk group, and disease‐stage are identified. However, epigenetic dysregulations also play major roles in the development of neuroblastoma. Patients gradually develop resistance to conventional chemotherapy or relapse occurs after treatment. New therapy approaches have been developed, either as alternatives to conventional chemotherapy, or in combination with it, in order to overcome the handicaps. Targeted therapies, those directly affecting the cancer cell or the cancer stem cell and having a minimal effect on healthy cells, constitute these approaches. Since neuroblastoma is highly heterogeneous both genetically and epigenetically, the data obtained from molecular mechanisms will greatly contribute to the survival of patients

Melatonin: a promising neuroprotective agent for cerebral ischemia-reperfusion injury

Cerebral ischemia-reperfusion (CIR) injury is initiated by the generation of reactive oxygen species (ROS), which leads to the oxidation of cellular proteins, DNA, and lipids as an initial event. The reperfusion process impairs critical cascades that support cell survival, including mitochondrial biogenesis and antioxidant enzyme activity. Failure to activate prosurvival signals may result in increased neuronal cell death and exacerbation of CIR damage. Melatonin, a hormone produced naturally in the body, has high concentrations in both the cerebrospinal fluid and the brain. However, melatonin production declines significantly with age, which may contribute to the development of age-related neurological disorders due to reduced levels. By activating various signaling pathways, melatonin can affect multiple aspects of human health due to its diverse range of activities. Therefore, understanding the underlying intracellular and molecular mechanisms is crucial before investigating the neuroprotective effects of melatonin in cerebral ischemia-reperfusion injury

Correlation between telomerase and mTOR pathway in cancer stem cells

WOS: 000416616300032PubMed ID: 29074462Cancer stem cells (CSCs), which are defined as a subset of tumor cells, are able to self -renew, proliferate, differentiate similar to normal stem cells. Therefore, targeting CSCs has been considered as a new approach in cancer therapy. The mammalian target of rapamycin (mTOR) is a receptor tyrosine kinase which plays an important role in regulating cell proliferation, differentiation, cell growth, self-renewal in CSCs. On the other hand, hTERT overactivation provides replicative feature and immortality to CSCs, so the stemness and replicative properties of CSCs depend on telomerase activity. Therefore hTERT/telomerase activity may become a universal biomarker for anticancer therapy and it is an attractive therapeutic target for CSCs. It is known that mTOR regulates telomerase activity at the translational and post -translational level. Researchers show that mTOR inhibitor rapamycin reduces telomerase activity without changing hTERT mRNA activity. Correlation between mTOR and hTERT is important for survival and immortality of cancer cells. In addition, the PI3K/AKT/mTOR signaling pathway and hTERT up-regulation are related with cancer stemness features and drug resistance. mTOR inhibitor and TERT inhibitor combination may construct a novel strategy in cancer stem cells and it can make a double effect on telomerase enzyme. Consequently, inhibition of PI3K/AKT/mTOR signaling pathway components and hTERT activation may prohibit CSC self-renewal and surpass CSC-mediated resistance in order to develop new cancer therapeutics

Molecular perspective on targeted therapy in breast cancer: a review of current status

Breast cancer is categorized at the molecular level according to the status of certain hormone and growth factor receptors, and this classification forms the basis of current diagnosis and treatment. The development of resistance to treatment and recurrence of the disease have led researchers to develop new therapies. In recent years, most of the research in the field of oncology has focused on the development of targeted therapies, which are treatment methods developed directly against molecular abnormalities. Promising advances have been made in clinical trials investigating the effect of these new treatment modalities and their combinations with existing therapeutic treatments in the treatment of breast cancer. Monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates, PI3K/Akt/mTOR pathway inhibitors, cyclin-dependent kinase 4/6 inhibitors, anti-angiogenic drugs, PARP inhibitors are among the targeted therapies used in breast cancer treatment. In this review, we aim to present a molecular view of recently approved target agents used in breast cancer