During cancer genesis, the extracellular matrix (ECM) in the human brain undergoes important transformations, starting to resemble embryonic brain cell milieu with a much denser structure. However, the stiffness of the tumor ECM does not preclude cancer cells from migration. The importance of the ECM role in normal brain tissue as well as in tumor homeostasis has engaged much effort in trials to implement ECM as a target and an instrument in the treatment of brain cancers. This review provides a detailed analysis of both experimental and applied approaches in combined therapy for gliomas in adults. In general, matrix materials for glioma treatment should have properties facilitating the simplest delivery into the body. Hence, to deliver an artificial implant directly into the operation cavity it should be packed into a gel form, while for bloodstream injections matrix needs to be in the form of polymer micelles, nanoparticles, etc. Furthermore, the delivered material should mimic biomechanical properties of the native tissue, support vital functions, and slow down or stop the proliferation of surrounding cells for a prolonged period. The authors propose a two-step approach aimed, on the one hand, at elimination of remaining cancer cells and on the other hand, at restoring normal brain tissue. Thereby, the first bioartificial matrix to be applied should have relatively low elastic modulus should be loaded with anticancer drugs, while the second material with a higher elastic modulus for neurite outgrowth support should contain specific factors stimulating neuroregeneration.
Skin cancer has always been and remains the leader among all tumors in terms of occurrence. One of the main factors responsible for skin cancer, natural and artificial UV radiation, causes the mutations that transform healthy cells into cancer cells. These mutations inactivate apoptosis, an event required to avoid the malignant transformation of healthy cells. Among these deadliest of cancers, melanoma and its ‘younger sister’, Merkel cell carcinoma, are the most lethal. The heavy toll of skin cancers stems from their rapid progression and the fact that they metastasize easily. Added to this is the difficulty in determining reliable margins when excising tumors and the lack of effective chemotherapy. Possibly the biggest problem posed by skin cancer is reliably detecting the extent to which cancer cells have spread throughout the body. The initial tumor is visible and can be removed, whereas metastases are invisible to the naked eye and much harder to eliminate. In our opinion, antisense oligonucleotides, which can be used in the form of targeted ointments, provide real hope as a treatment that will eliminate cancer cells near the tumor focus both before and after surgery.
Cellular quiescence is a reversible, non-cycling state controlled by epigenetic, transcriptional and niche-associated molecular factors. Quiescence is a condition where molecular signaling pathways maintain the poised cell-cycle state whilst enabling rapid cell cycle re-entry. To achieve therapeutic breakthroughs in oncology it is crucial to decipher these molecular mechanisms employed by the cancerous milieu to control, maintain and gear stem cells towards re-activation. Cancer stem-like cells (CSCs) have been extensively studied in most malignancies, including glioma. Here, the aberrant niche activities skew the quiescence/activation equilibrium, leading to rapid tumor relapse after surgery and/or chemotherapy. Unraveling quiescence mechanisms promises to afford prevention of (often multiple) relapses, a key problem in current glioma treatment. This review article covers the current knowledge regarding normal and aberrant cellular quiescence control whilst also exploring how different molecular mechanisms and properties of the neighboring cells can influence the molecular processes behind glioma stem cell quiescence.
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