Magyar onkologia最新文献

With the advancement of molecular oncology, numerous new opportunities are available for the effective and efficient treatment of patients diagnosed with childhood brain tumors. This includes gene panel analysis aiding personalized treatment used in clinical trials, and the application of targeted therapy independent of tissue type (tumor agnostic therapy). Most personalized therapies inhibit certain kinases. In our review, we present the modern pathological diagnosis of childhood brain tumors, as well as the complex intracellular regulation of signal transduction pathways important from the point of view of clinical practice, and we describe their further targets defined on the basis of pharmacological characteristics of the pathway, based on international and our own results. Despite common mutations affecting kinases, personalized therapy is not available in many types of tumors. Through the example of childhood brain tumors, we demonstrate the expected future therapeutic significance of tyrosine kinases.

Recent advances in molecular diagnostics are transforming the classification of malignant tumours, it has long played a major role in the field of CNS tumours. Examination of 1p/19q codeletion is indispensable in case of diffuse gliomas. Glioblastoma may be diagnosed even in the absence of characteristic morphological features, when EGFR amplification, TERT promoter mutation or +7/-10 copy number abnormalities are present. The number of entities defined by a genetic abnormality is growing. Comprehensive analysis of DNA methylation may be of considerable help in addition to histology and basic molecular studies, especially in case of small samples. Keeping up with the ever-expanding diagnostic repertoire is difficult, however, advantages and disadvantages of these methods and the context in which they may be useful should be understood by those who are involved in the diagnosis of CNS tumours. This summary provides a general overview of the main methods used in molecular diagnostics.

The appearance of hybrid imaging, including PET/CT has been a huge milestone not only in the development of nuclear medicine but of the whole medical imaging. The examination with 18F-FDG, the most frequently used radiopharmaceutical has become for now one of the most important diagnostic tools in oncological patient care, applied with numerous indication goals. However, the depiction of central nervous system malignancies, especially those of the brain, with FDG PET has limitations due to high cerebral background activity, it can be used primarily in lymphoma cases. To evaluate gliomas and brain metastases, amino acid tracers (11C-methionine, 18F-DOPA and 18F-FET) gained ground, which reflect other biological processes compared to that of FDG. Upon multiplying of evidences their usage is becoming more and more diverse, from the primary assessment of brain tumours (benign vs. malignant), through their grading and evaluation of posttherapeutical viability/recurrence, up to the radiotherapy planning. This paper reviews all of these in more details, mentioning shortly the prospects and challenges of the future.

Considerable changes were introduced into the 5th World Health Organization (WHO) classification of central nervous system (CNS) tumors, published in 2021, including new entities, a clearer classification of previous categories, correlating better with clinical behavior and changes in nomenclature. The number of definitions based on molecular features in addition to histopathology continued to increase. Here, we highlight the basic principles of the 5th CNS WHO classification and discuss glial, glioneuronal, neuronal, choroid plexus, embryonal and pineal tumors, as well as meningiomas in more details. We pay special attention to new entities as well as altered criteria and designations. Our primary goal is to present the "classical" pathological aspects, but the inseparable molecular pathological features are also briefly discussed, to the absolutely necessary extent for comprehension. We aim to provide a guideline to understand the modern classification of CNS tumors for practitioners of neuro-oncology and neuropathology.

The occurrence of central nervous system malignancies is relatively low; however, these tumors exhibit poor prognosis and a high mortality rate. On epidemiological grounds, Hungary was placed in the last third among European countries: in the last decade annually 750 to 1000 new cases were diagnosed and the number of deaths was between 550 and 690, without any apparent trends. Age distribution analyses revealed childhood peak and a higher peak at around 65 years of age. Histologically, heterogeneity was apparent, but at least half of the cases were glioblastomas. The exact etiology of adulthood brain tumors is mostly unknown. Among environmental exposures the effect of ionizing radiation was confirmed, the identification of other potential risk factors requires further examinations. 7-10 percent of brain tumors were hereditary tumor syndromes (Li-Fraumeni, neurofibromatosis, sclerosis tuberosa, von Hippel-Lindau, Gorlin- Goltz). Therefore, genetic testing is recommended for families where the diagnosis of brain tumor is suspected.

A frequently recommended systemic therapy for breast cancer involves a combination of anthracyclines and taxanes, however, approximately 30% of patients experience recurrence. We aimed to investigate the mechanisms of resistance to anthracycline-paclitaxel based treatment by analyzing gene expression patterns in tumor samples collected during surgery and subsequent therapeutic responses. A database of 187 patients with information about relapse-free survival (RFS) allowed the analysis of 10,017 genes. Patients were divided into responders and nonresponders based on whether relapse occurred within sixty months. The expression of each gene was compared between the two groups using the Mann-Whitney U-test, with a statistical significance set at p <0.05 and fold change (FC) ≥1.44. We identified 51 up-regulated genes among nonresponders, primarily associated with inflammatory processes and the innate immune response. The high expression of SLC7A5, encoding an amino acid transporter, was linked to worse overall survival (p = 2.3E-10), with elevated expression in tumors (p = 2.94E-20), and further increase in metastases (p = 1.33E-10). Our results emphasize the significance of tumor microenvironment and metabolism in therapy resistance. These findings may allow better patient classification and identification of relevant treatment targets.

The treatment of advanced-stage pancreatic cancers is limited. Previous studies have found that the use of modulated electro-hyperthermia (mEHT) is beneficial in this patient population. However, there is no data on the optimal treatment number and initiation period. Therefore, a retrospective study was conducted with the inclusion of 96 mEHT-treated and 86 age- and sex-matched control pancreatic cancer patients. 76, 57, 38 and 33 patient pairs were enrolled into propensity score matched cohorts, whether they received at least 10, 20, 30 and 40 mEHT treatments, respectively. The survival of patients with at least 30 (HR: 0.5011; p = 0.0041) and 40 (HR: 0.5048; p = 0.0085) mEHT treatments was significantly longer, median survival was almost twice as long (10 vs. 18 months). The introduction of mEHT had the greatest benefit in the first (HR: 0.5382; p = 0.0056) and second (HR: 0.7861; p = 0.0031) 6 months after diagnosis.

The issues surrounding the cost effectiveness of drug development and the ethical concerns associated with animal testing, emphasise the necessity for innovative in vitro models that allow enhanced pre-selection. Therefore, we aim to create 3D bioprinted tissue mimetic structures (TMS) utilizing various human cancer cell lines. We have generated TMSs from human tumour cell lines (breast, kidney, glioma), with detailed characterisation of the ZR75.1 cell line. In this study, the tissue heterogeneity, the growth rate, and the drug sensitivity of different in vitro and in vivo models were compared. Tissue formation occurs within the TMS after one week, with a tissue heterogeneity similar to in vivo growing tumours. Moreover, TMSs exhibit similar drug sensitivity to that observed in vivo. In summary, the established 3D bioprinted TMSs represent an advanced in vitro model, which can contribute to achieve a more effective and ethical drug development process in the field of oncology.

Small-cell lung cancer (SCLC) is a highly aggressive malignancy characterised by genomic instability and early metastatic spread. Patients are typically diagnosed at advanced disease stage, when platinum-based chemotherapy with immunotherapy represents the standard therapeutic approach. The role of radiotherapy with concomitant systemic therapy is also well established in the management of SCLC patients. Although these therapeutic approaches are initially effective, most patients rapidly develop resistance. This clearly highlights the need to improve therapeutic efficacy and broaden the scope of current therapeutic strategies. Recent advances in the study of this disease, once considered homogeneous, have led to a new model of the SCLC classification scheme based on the relative expression of certain transcriptional regulators and inflammatory characteristics. New biological insights into the molecular subtypes of SCLC could lead to the implementation of subtype-specific therapeutic approaches. Here, we summarise our key findings concerning the biological and clinical relevance of SCLC molecular subtypes.

Failures of anti-tumour therapies and drug resistance initiate difficulties in cancer treatments often caused by alterations in signalling network activity, including PI3K/Akt/mTOR hyperactivity due to oncogenic mutations. In this review, we summarise the relevance of mTOR (mechanistic target of rapamycin) dysregulation identified decades ago, which is now known to be characteristic of many tumours. In this context, we present differences in activity, function and testability of mTOR kinase complexes (mTORC1 and mTORC2) differing in structure, regulatory mechanisms and inhibitor sensitivity. We highlight that genetic alterations, including RICTOR amplification and associated mTOR hyperactivity, are relevant in targeted therapy development. It is recommended to investigate mTOR profile activity in patients for whom mTOR inhibitor therapies are considered since the current first-generation mTOR inhibitors (rapamycin and analogues) may be ineffective in case of mTORC2 hyperactivity. Ongoing phase trials of new inhibitors and combination therapies are promising in advanced stage patients selected by molecular markers.