The Role of Mammalian Target of Rapamycine Signaling Pathway in Central Nervous System Cancers: A Review

Mammalian mechanistic target of rapamycine (mTOR) is a conserved serine/threonine kinase in the cellular PI3K/Akt/mTOR signaling pathway. This pathway is modified by cellular alterations such as level of energy, growth factors, stresses, as well as the increased environmental level of cancerous cytokines. In general, increase of this kinase protein function is seen in various types of cancers, especially in cancer stem-like cell. Additionally, activation of this pathway in the most common malignant central nervous system cancers such as glioblastoma, medulloblastomas and tuberous sclerosis complex is under investigation. Recent studies have shown the relationship between different cellular signaling pathways and genetic mutations, that involved in the cancer of CNS, with mTOR pathway. Based on previous studies, different treatments like surgery, chemotherapy, radiotherapy, aren’t more effective and have some side-effects. Therefore, the researchers are trying to find better ways to treat cancer. One approach to this aim is about the essence of understanding all of molecular pathways, proteins and mutations involved in cancers. This study tries to analysis some of the unknown molecular pathways on mentioned cancerous cells and interaction among this pathway with mTOR kinase protein.

Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.

The Role of Liquid Biopsies in Detecting Molecular Tumor Biomarkers in Brain Cancer Patients

Glioblastoma multiforme (GBM) is one of the most lethal primary central nervous system cancers with a median overall survival of only 12–15 months. The best documented treatment is surgical tumor debulking followed by chemoradiation and adjuvant chemotherapy with temozolomide, but treatment resistance and therefore tumor recurrence, is the usual outcome. Although advances in molecular subtyping suggests GBM can be classified into four subtypes, one concern about using the original histology for subsequent treatment decisions is that it only provides a static snapshot of heterogeneous tumors that may undergo longitudinal changes over time, especially under selective pressure of ongoing therapy. Liquid biopsies obtained from bodily fluids like blood and cerebro-spinal fluid (CSF) are less invasive, and more easily repeated than surgery. However, their deployment for patients with brain cancer is only emerging, and possibly suppressed clinically due to the ongoing belief that the blood brain barrier prevents the egress of circulating tumor cells, exosomes, and circulating tumor nucleic acids into the bloodstream. Although brain cancer liquid biopsy analyses appear indeed challenging, advances have been made and here we evaluate the current literature on the use of liquid biopsies for detection of clinically relevant biomarkers in GBM to aid diagnosis and prognostication.

Recent Advances on Antitumor Agents-loaded Polymeric and Lipid-based Nanocarriers for the Treatment of Brain Cancer

In 2016, there were 17.2 million cancer cases, which caused 8.9 million deaths worldwide. Of all cancers, ranked by absolute years of life lost, brain and central nervous system cancers were classified in the nine positions between 2006 and 2016. Glioblastoma is the most common malignant primary brain tumor and comprises 80% of malignant tumours. The therapeutic approach usually involves the combination of surgery and radiotherapy, which present a high risk for the patient and are not always effective in the most aggressive cases. Chemotherapy commonly includes a specific number of cycles given over a set period of time, in which patients receive one drug or a combination of different compounds. The difficulty of access for the neurosurgeon to remove the tumor, the limitation of the penetration of the antitumor agents caused by the blood-brain barrier and the serious adverse effects of these drugs significantly compromise the therapeutic success in these patients. To solve these problems and improve the effectiveness of existing treatments, as well as new molecules, the use of nanotechnology is arousing much interest in the last decades in this field. The use of polymeric and lipid-based nanosystems is one of the best alternatives for the central delivery of drugs due to their versatility, easy manufacturing, biocompatibility, biodegradability and drug targeting, among other virtues. Thus, in this review, we will explore the recent advances in the latest anticancer agent’s development associated with polymeric and lipid-based nanocarriers as a novel tools for the management of brain tumors.