Despite all of the progress in understanding its molecular biology and pathogenesis, glioblastoma (GBM) is one of the most aggressive types of cancers, and without an efficient treatment modality at the moment, it remains largely incurable. Nowadays, one of the most frequently studied molecules with important implications in the pathogenesis of the classical subtype of GBM is the epidermal growth factor receptor (EGFR). Although many clinical trials aiming to study EGFR targeted therapies have been performed, none of them have reported promising clinical results when used in glioma patients. The resistance of GBM to these therapies was proven to be both acquired and innate, and it seems to be influenced by a cumulus of factors such as ineffective blood–brain barrier penetration, mutations, heterogeneity and compensatory signaling pathways. Recently, it was shown that EGFR possesses kinase-independent (KID) pro-survival functions in cancer cells. It seems imperative to understand how the EGFR signaling pathways function and how they interconnect with other pathways. Furthermore, it is important to identify the mechanisms of drug resistance and to develop better tailored therapeutic agents.

Glioblastoma stem cells (GSCs) are cells with a self-renewal ability and capacity to initiate tumors upon serial transplantation that have been linked to tumor cell heterogeneity. Most standard treatments fail to completely eradicate GSCs, causing the recurrence of the disease. GSCs could represent one reason for the low efficacy of cancer therapy and for the short relapse time. Nonetheless, experimental data suggest that the presence of therapy-resistant GSCs could explain tumor recurrence. Therefore, to effectively target GSCs, a comprehensive understanding of their biology and the survival and developing mechanisms during treatment is mandatory. This review provides an overview of the molecular features, microenvironment, detection, and targeting strategies of GSCs, an essential information required for an efficient therapy. Despite the outstanding results in oncology, researchers are still developing novel strategies, of which one could be targeting the GSCs present in the hypoxic regions and invasive edge of the glioblastoma.

The race to find an effective treatment for glioblastoma (GBM) remains a critical topic, because of its high aggressivity and impact on survival and the quality of life. Currently, due to GBM’s high heterogeneity, the conventional treatment success rate and response to therapy are relatively low, with a median survival rate of less than 20 months. A new point of view can be provided by the comprehension of the tumor microenvironment (TME) in pursuance of the development of new therapeutic strategies to aim for a longer survival rate with an improved quality of life and longer disease-free interval (DFI). The main components of the GBM TME are represented by the extracellular matrix (ECM), glioma cells and glioma stem cells (GSCs), immune cells (microglia, macrophages, neutrophils, lymphocytes), neuronal cells, all of them having dynamic interactions and being able to influence the tumoral growth, progression, and drug resistance thus being a potential therapeutic target. This paper will review the latest research on the GBM TME and the potential therapeutic targets to form an up-to-date strategy.

Glioblastoma is known to be one of the most aggressive and fatal human cancers, with a poor prognosis and resistance to standard treatments. In the last few years, many solid tumor treatments have been revolutionized with the help of immunotherapy. However, this type of treatment has failed to improve the results in glioblastoma patients. Effective immunotherapeutic strategies may be developed after understanding how glioblastoma achieves tumor-mediated immune suppression in both local and systemic landscapes. Biomarkers may help identify patients most likely to benefit from this type of treatment. In this review, we discuss the use of immunotherapy in glioblastoma, with an emphasis on immune checkpoint inhibitors and the factors that influence clinical response. A Pubmed data search was performed for all existing information regarding immune checkpoint inhibitors used for the treatment of glioblastoma. All data evaluating the ongoing clinical trials involving the use of ICIs either as monotherapy or in combination with other drugs was compiled and analyzed.

The most commonly diagnosed malignancy of the urinary system is represented by renal cell carcinoma. Various subvariants of RCC were described, with a clear-cell type prevailing in about 85% of all RCC tumors. Patients with metastases from renal cell carcinoma did not have many effective therapies until the end of the 1980s, as long as hormonal therapy and chemotherapy were the only options available. The outcomes were unsatisfactory due to the poor effectiveness of the available therapeutic options, but then interferon-alpha and interleukin-2 showed treatment effectiveness, providing benefits but only for less than half of the patients. However, it was not until 2004 that targeted therapies emerged, prolonging the survival rate. Currently, new technologies and strategies are being developed to improve the actual efficacy of available treatments and their prognostic aspects. This article summarizes the mechanisms of action, importance, benefits, adverse events of special interest, and efficacy of immunotherapy in metastatic renal cell carcinoma, with a focus on brain metastases.

Background: While acknowledging the generally poor prognostic features of brain metastases from renal cell carcinoma (BM RCC), it is important to be aware of the fact that neurosurgery still plays a vital role in managing this disease, even though we have entered an era of targeted therapies. Notwithstanding their initial high effectiveness, these agents often fail, as tumors develop resistance or relapse. Methods: The authors of this study aimed to evaluate patients presenting with BM RCC and their outcomes after being treated in the Neurosurgical Department of Clinical Emergency Hospital “Bagdasar-Arseni”, and the Neurosurgical Department of the National Institute of Neurology and Neurovascular Diseases, Bucharest, Romania. The study is based on a thorough appraisal of the patient’s demographic and clinicopathological data and is focused on the strategic role of neurosurgery in BM RCC. Results: A total of 24 patients were identified with BM RCC, of whom 91.6% had clear-cell RCC (ccRCC) and 37.5% had a prior nephrectomy. Only 29.1% of patients harbored extracranial metastases, while 83.3% had a single BM RCC. A total of 29.1% of patients were given systemic therapy. Neurosurgical resection of the BM was performed in 23 out of 24 patients. Survival rates were prolonged in patients who underwent nephrectomy, in patients who received systemic therapy, and in patients with a single BM RCC. Furthermore, higher levels of hemoglobin were associated in our study with a higher number of BMs. Conclusion: Neurosurgery is still a cornerstone in the treatment of symptomatic BM RCC. Among the numerous advantages of neurosurgical intervention, the most important is represented by the quick reversal of neurological manifestations, which in most cases can be life-saving.