Although the term ‘cancer’ was still over two thousand years away of being coined, the first known cases of the disease date back to about 3000BC, in ancient Egypt. Five thousand years later, still lacking a cure, it has become one of the leading causes of death, killing over half a dozen million people yearly. So far, monoclonal antibodies are the most successful immune-therapy tools when it comes to fighting cancer. The number of clinical trials that use them has been increasing steadily during the past few years, especially since the Food and Drug Administration greenlit the use of the first immune-checkpoint blockade antibodies. However, albeit successful, this approach does come with the cost of auto-inflammatory toxicity. Taking this into account, the development of new therapeutic reagents with low toxicity becomes evident, particularly ones acting in tandem with the tools currently at our disposal. Ever since its discovery in the early nineties, aptamer technology has been used for a wide range of diagnostic and therapeutic applications. With similar properties to those of monoclonal antibodies, such as high-specificity of recognition and high-affinity binding, and the advantages of being developed using in vitro selection procedures, aptamers quickly became convenient building blocks for the generation of multifunctional constructs. In this review, we discuss the steps involved in the in vitro selection process that leads to functional aptamers - known as Systematic Evolution of Ligands by Exponential Enrichment - as well as the most recent applications of this technology in diagnostic and treatment of oncological illnesses. Moreover, we also suggest ways to improve such use.

Tumour progression involves interactions among various cancer cell clones, including the cancer stem cell subpopulation and exogenous cellular components, termed cancer stromal cells. The latter include a plethora of tumour infiltrating immunocompetent cells, among which are also immuno-modulatory mesenchymal stem cells, which by vigorous migration to growing tumours and susequent transdifferentiation into various types of tumour-residing stromal cells, may either inhibit or support tumour progression. In the light of the scarce therapeutic options existing for the most malignant brain tumour glioblastoma, mesenchymal stem cells may represent a promising novel tool for cell therapy, e.g. drug delivery vectors. Here, we review the increasing number of reports on mutual interactions between mesenchymal stem cells and glioblastoma cells in their microenvironment. We particularly point out two novel aspects: the different responses of cancer cells to their microenvironmental cues, and to the signalling by kinin receptors that complement the immuno-modulating cytokine-signalling networks. Inflammatory glioblastoma microenvironment is characterised by increasing expression of kinin receptors during progressive glioma malignancy, thus making kinin signalling and kinins themselves rather important in this context. In general, their role in tumour microenvironment has not been explored so far. In addition, kinins also regulate blood brain barrier-related drug transfer as well as brain tumour angiogenesis. These studies support the ongoing research on kinin antagonists as candidates in the development of anti-invasive agents for adjuvant glioblastoma therapy. Keywords Co-culture. Glioma. Kinin receptors. Mesenchymal stem cells. Microenvironment. Tumour heterogeneity Brain Tumours-Glioblastoma Brain tumours originate from various types of cells, of which astroglial tumours being the most frequent. The World Health Organisation (WHO) distinguishes four grades of glioma, of which glioblastoma (GBM) is the most aggressive, invasive, and lethal among all types of brain tumours. Unfortunately, it is also the most common among glial tumours with 5-7 cases per 100.000 individuals yearly, and represents 50% of all gliomas [1, 2]. It is characterised by histological features such as necrosis, vascular proliferation and pleomorphism. Contrary to most tumour types, irradiation and chemotherapy has proven to be ineffective to impair long term GBM progression, demonstrating its remarkable therapeutic resistance [3-5]. Radiotherapy is combined with chemotherapy, for which the alkylating agent temozolomide has been used in most cases. There is a constant search for novel adjuvant therapeutics, including kinase inhibitors, anti-angiogenic agents and recently also immunotherapy to increase average survival of GBM patients. Several reasons for GBM resistance to therapy has been recognised, such as diffuse infiltration of cancer cells into neighbouring brain parenchyma that are hard to target by surgery [6-8]. Furthermore, the presence of het...

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