In 2016, the WHO introduced new guidelines for the diagnosis of brain gliomas based on new genomic markers. The addition of these new markers to the pre-existing diagnostic methods provided a new level of precision for the diagnosis of glioma and the prediction of treatment effectiveness. Yet, despite this new classification tool, glioblastoma (GBM), a grade IV glioma, continues to have one of the highest mortality rates among central nervous system tumors. Metabolomics is a particularly promising tool for the analysis of GBM tumors and potential methods of treating them, as it is the only “omics” approach that is capable of providing a metabolic signature of a tumor’s phenotype. With careful experimental design, cell cultures can be a useful matrix in GBM metabolomics, as they ensure stable conditions and, under proper conditions, are capable of capturing different tumor phenotypes. This paper reviews in vitro metabolomic profiling studies of high-grade gliomas, with a particular focus on sample-preparation techniques, crucial metabolites identified, cell culture conditions, in vitro-in vivo extrapolation, and pharmacometabolomics. Ultimately, this review aims to elucidate potential future directions for in vitro GBM metabolomics.

The growing interest of oncologists in natural compounds such as polyphenols and flavonoids is encouraging the development of innovative and efficient carriers for the delivery of those drugs. This study examines carboxymethyl chitosan-based microcapsules created by spray drying as a method for delivering biologically active compounds isolated from the Cistus herb. Effects of sterilization and encapsulation on the polyphenol and flavonoid content of Cistus extract were investigated to optimize the production process. Furthermore, in vitro studies were carried out to examine the anticancer properties of sterilized polyphenols and flavonoids on glioblastoma cells isolated from oncological patients. Acquired results show high anticancer potential towards glioblastoma as well as low cytotoxicity towards non-cancer cell lines by the substances in question. Steam sterilization is shown to affect the content of biologically active compounds the least. We demonstrate that the investigated form of drug encapsulation is both efficient and potentially possible to scale up from the viewpoint of the pharmaceutical industry. According to apress statement launched by the International Agency for Research on Cancer from the World Health Organization (WHO), in 2018the global cancer burdenaffected 18.1 million new cases and 9.6 million of people passed away. Ten in 50 men and one in 60 women worldwide suffer from cancer during their life, and ten in 80 men and eleven in 110 women posse awaydue to thisillness. Moreover, cancer is a most frequent causeof children death. Worldwide, every year, approximately 300.000 of children are diagnosed by oncologists with a cancer disease 1,2. Furthermore, according to the published statistic data, the total number of people who are alive within 5 years of a cancer diagnosis, called the 5-year prevalence, is arround 43.8 million 3. As stated in the WHO report,the frequent types of cancer in men are cancer of lung, prostate, colorectal, stomach and liver, while in case on women, the most common type of cancer are: breast, colorectal, lung, cervix and thyroid cancer. The uncontrollable growth of tumor cells is the most fundamental aspect of cancer 4. Even if available therapies such as surgery, immunotherapy, chemotherapy, targeted therapy, hormone therapy and radiation therapy play a significant role in cancer treatment, drug resistance and toxicity remain main problems and challenges to cure cancer patients 5. Oncologists have called for basic investigationsand new upstream technologieswhich insustainably, efficiently and safely way will meet the current and future patients' needs 6,7. Additionally, during the last years the "integrative" oncology society has demanded advancesfrom scientists on the development of natural medicals 8,9. Indeed, the anticancer effects of biologically active compounds, such as natural polyphenols synthesized by fruits, vegetables, teas, apples, cocoa and other plants, have become a hot topic in many laboratories 10-12 .

Personalized medicine is an extension of traditional medicine is based on a highly individual approach to each patient. One of the most important tools that allow this approach is targeted therapy. It focuses mainly on blocking cancer cell's proliferation and angiogenesis capabilities by interfacing with specific molecules that are involved in the growth and progression of the tumour. Small-molecule inhibitors and monoclonal antibodies are the main drugs that are currently in use in order to affect the specific biochemical pathways in cancer cells. However, likewise any other cancer therapies, targeted therapy has its own limitations. For instance, identifying a molecular target needed to begin treatment is one of those hardships. A specific molecule is crucial in this way of treatment. The other limitation is the toxicity that appears during the treatment, the same as in the case of traditional chemotherapy and radiotherapy. Furthermore, the cost of this therapy is significantly higher compared to classical treatments. However, the main obstacles are mechanisms of cancer drug resistance which are often developing in response to given drugs. In many cases, it makes further treatment impossible. This article is focusing on the limitations of molecularly targeted therapy.