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Topic Review
Three-Dimensional In Vitro Cell Models of HNSCC
Researchers have been trying to answer the demand of clinical oncologists to create an ideal preclinical model of head and neck squamous cell carcinoma (HNSCC) that is accessible, reproducible, and relevant. Over the past, the development of cellular technologies has naturally allowed people to move from primitive short-lived primary 2D cell cultures to complex patient-derived 3D models that reproduce the cellular composition, architecture, mutational, or viral load of native tumor tissue. Depending on the tasks and capabilities, a scientific laboratory can choose from several types of models: primary cell cultures, immortalized cell lines, spheroids or heterospheroids, tissue engineering models, bioprinted models, organoids, tumor explants, and histocultures. HNSCC in vitro models make it possible to screen agents with potential antitumor activity, study the contribution of the tumor microenvironment to its progression and metastasis, determine the prognostic significance of individual biomarkers (including using genetic engineering methods), study the effect of viral infection on the pathogenesis of the disease, and adjust treatment tactics for a specific patient or groups of patients. 
  • 507
  • 20 Nov 2023
Topic Review
Chronic Inflammatory States and Altered Conditions in Tumors
In tumor cells, enhanced levels of cytotoxic agents are usually counteracted by an overexpression of protective mechanisms. In this manner, tumor cells can even survive therapeutically induced stress situations. Tumor cells also affect immune cells and other cells in their close neighborhood in such a way that cells in this tumor microenvironment change their properties and promote tumor progression. Numerous examples are given for how the disturbed balance between inflammation-associated cytotoxic agents and antagonizing principles is related to tumor growth, tumor cell invasion, and metastasis.
  • 507
  • 09 Jan 2024
Topic Review
PPARγ Modulators in Lung Cancer
Lung cancer is one of the most lethal malignancies worldwide. Peroxisome proliferator-activated receptor gamma (PPARγ, NR1C3) is a ligand-activated transcriptional factor that governs the expression of genes involved in glucolipid metabolism, energy homeostasis, cell differentiation, and inflammation. Multiple studies have demonstrated that PPARγ activation exerts anti-tumor effects in lung cancer through regulation of lipid metabolism, induction of apoptosis, and cell cycle arrest, as well as inhibition of invasion and migration. Interestingly, PPARγ activation may have pro-tumor effects on cells of the tumor microenvironment, especially myeloid cells. Recent clinical data has substantiated the potential of PPARγ agonists as therapeutic agents for lung cancer. Additionally, PPARγ agonists also show synergistic effects with traditional chemotherapy and radiotherapy. However, the clinical application of PPARγ agonists remains limited due to the presence of adverse side effects.
  • 507
  • 26 Feb 2024
Topic Review
Checkpoint Inhibition in Bladder Cancer
In contrast with other strategies, immunotherapy is a treatment aimed at empowering the patient’s immune system in order to increase immunity and the response against cancer. A new class of drugs, immune checkpoint inhibitors, has shown potential in increasing treatment chances for patients with bladder cancers, improving their survival. However, predicting the response to immune checkpoint inhibition is important, since only a group of patients develop a good response. Biomarkers to predict the response to checkpoint inhibition must identify tumors’ and patients’ specific profiles. 
  • 506
  • 30 Jan 2022
Topic Review
TP53 Regulation of Cell Survival and Apoptosis
The new biological interaction cross-section-based repairable–homologically repairable (RHR) damage formulation for radiation-induced cellular inactivation, repair, misrepair, and apoptosis was applied to optimize radiation therapy. This new formulation accurately describing the cell survival and apoptosis and implies renewed thinking about biologically optimized radiation therapy, suggesting that most TP53 intact normal tissues are low-dose hypersensitive (LDHS) and low-dose apoptotic (LDA). This generates a fractionation window in LDHS normal tissues, indicating that the maximum dose to organs at risk should be ≤2.3 Gy/Fr, preferably of low LET. This calls for biologically optimized intensity modulated treatments using a few high tumor dose photon or light ion beams, preferably lithium to boron ion thereby avoiding secondary cancer risks and generating true tumor cure without risk for caspase-3-induced accelerated tumor cell repopulation.
  • 506
  • 04 Sep 2023
Topic Review
Intratumoral Stromal Content in Lobular Breast Cancer
High intratumoral stromal content is related to worse outcomes in several types of cancer. However, its prognostic role in breast cancer seems to differ between different subtypes. High intratumoral stromal content is a negative prognostic marker in triple-negative breast cancer, while the opposite is the case for estrogen-receptor-positive breast cancer, in which higher stromal content is indicative of a better prognosis. Most lobular breast cancers are estrogen-receptor-positive, and the tumor tissue has a clearly defined histological appearance, often with a high intratumoral stromal content. 
  • 505
  • 18 Feb 2022
Topic Review
dMMR/MSI-High Gastrointestinal Cancers
Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response seen with immune checkpoint inhibitors (ICIs), which are orchestrated by MANA-primed effector T cells, resulted in the rapid development of these novel therapeutics within the landscape of MSI-H gastrointestinal cancers.
  • 504
  • 08 Aug 2023
Topic Review
Angiogenesis in Cancer and Its Therapeutic Targeting
Vascular endothelial growth factors (VEGFs) are the key regulators of vasculogenesis in normal and oncological development. VEGF-A is the most studied angiogenic factor secreted by malignant tumor cells under hypoxic and inflammatory stress, which made VEGF-A a rational target for anticancer therapy. However, inhibition of VEGF-A by monoclonal antibody drugs led to the upregulation of VEGF-D. VEGF-D was primarily described as a lymphangiogenic factor; however, VEGF-D’s blood angiogenic potential comparable to VEGF-A has already been demonstrated in glioblastoma and colorectal carcinoma. These findings suggested a role for VEGF-D in facilitating malignant tumor growth by bypassing the anti-VEGF-A antiangiogenic therapy. Owing to its high mitogenic ability, higher affinity for VEGFR-2, and higher expression in cancer, VEGF-D might even be a stronger angiogenic driver and, hence, a better therapeutic target than VEGF-A.
  • 504
  • 11 Sep 2023
Topic Review
Autophagy Modulation Mechanism and Application
Autophagy is a vital cellular process that functions to degrade and recycle damaged organelles into basic metabolites. This allows a cell to adapt to a diverse range of challenging conditions. Autophagy assists in maintaining homeostasis, and it is tightly regulated by the cell. The disruption of autophagy has been associated with many diseases, such as neurodegenerative disorders and cancer. 
  • 504
  • 01 Nov 2023
Topic Review
Hereditary Prostate Cancer
Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits.
  • 502
  • 25 May 2021
Topic Review
Targeting Angiogenesis in Prostate Cancer
Prostate cancer is the most commonly diagnosed cancer among men in the Western world. Although localized disease can be effectively treated with established surgical and radiopharmaceutical treatments options, the prognosis of castration-resistant advanced prostate cancer is still disappointing.
  • 501
  • 27 Jan 2022
Topic Review
Dichotomy of Urinary Proteins
Urinary biomarkers offer non-invasive avenues for detecting cancers, potentially bypassing the invasiveness of biopsies. The investigation focuses primarily on breast and prostate cancers due to their prevalence among women and men, respectively. The intricate interplay of urinary proteins is explored, revealing a landscape where proteins exhibit context-dependent behaviors. 
  • 501
  • 22 Jan 2024
Topic Review
DNA Methylation and Melanoma
Malignant melanoma is the most lethal form of skin cancer. While new therapeutic approaches have improved survival in patients with metastatic melanoma, responses are rarely sustained due to the high degree of heterogeneity at the inter- and intra-metastatic levels. The development of reliable biomarkers to monitor therapeutic response and disease progression is critical. Many aberrantly methylated genes play a role in cell cycle control, apoptosis, and cell invasion, as well as in melanoma progression. Longitudinal monitoring of DNA methylation via liquid biopsy can provide real-time information on the behavior and stage of melanoma.
  • 500
  • 27 Dec 2021
Topic Review
Radiation Oncology and Surgery for Brain Metastases Management
Brain metastases are of increasing concern in the management of cancer patients. New systemic treatment options like specific targeting agents or immune checkpoint inhibitors allow for longer survival with a higher incidence of brain metastases over the course of the disease. Single or a few small, asymptomatic lesions are mainly treated with focal stereotactic radiotherapy. On the other hand, in many cases, large and, in particular, symptomatic metastases require microsurgical resection for immediate symptom relief.
  • 500
  • 26 Jul 2023
Topic Review
Adoptive Cellular Therapies in Ovarian Cancer
Ovarian cancers are typically poorly immunogenic and have demonstrated disappointing responses to immune checkpoint inhibitor (ICI) therapy. Adoptive cellular therapy (ACT) offers an alternative method of harnessing the immune system that has shown promise, especially with the success of chimeric antigen receptor T-cell (CAR-T) therapy in haematologic malignancies. ACT has led to modest results in the treatment of solid organ malignancies. 
  • 500
  • 17 Oct 2023
Topic Review
ErbB Receptors in Endometrial Cancer
In EC, the expression of ErbB receptors is significantly different, compared with the premenopausal and postmenopausal endometrium, mainly because of the increased transcriptional activity of ErbB encoding genes in EC cells. Moreover, there are some differences in ErbB-2 receptor profile among EC subgroups that could be explained by the alterations in pathophysiology and clinical behavior of various EC histologic subtypes. The fact that ErbB-2 receptor expression is more common in aggressive EC histologic subtypes (papillary serous and clear cell) could indicate a future role of ErbB-targeted therapies in well-defined EC subgroups with overexpression of ErbB receptors.
  • 498
  • 16 Oct 2023
Topic Review
Next-Generation Sequencing's Application in ctDNA Detection and Quantification
Circulating tumour DNA (ctDNA) facilitates longitudinal study of the tumour genome, which, unlike tumour tissue biopsies, globally reflects intratumor and intermetastatis heterogeneity. Despite its costs, next-generation sequencing (NGS) has revolutionised the study of ctDNA, ensuring a more comprehensive and multimodal approach, increasing data collection, and introducing new variables that can be correlated with clinical outcomes. Current NGS strategies can comprise a tumour-informed set of genes or the entire genome and detect a tumour fraction as low as 10−5.
  • 498
  • 20 Feb 2024
Topic Review
Pituitary Function following Peptide Receptor Radionuclide Therapy
Pituitary neuroendocrine tumours (PitNETs) are usually benign and slow-growing; however, in some cases, they may behave aggressively and become resistant to conventional treatments. Therapeutic options for aggressive or metastatic PitNETs are limited, and currently mainly consist of temozolomide, with little experience of other emerging approaches, including peptide receptor radionuclide therapy (PRRT). Somatostatin receptor expression in PitNETs explains the effectiveness of somatostatin analogues for treating PitNETs, particularly those hypersecreting pituitary hormones, such as growth hormone or adrenocorticotropic hormone. The expression of such receptors in pituitary tumour cells has provided the rationale for using PRRT to treat patients with aggressive or metastatic PitNETs.
  • 496
  • 22 May 2023
Topic Review
Automated Blood Vessel Detection in Cancer
The analysis of the microvasculature and the assessment of angiogenesis have significant prognostic value in various diseases, including cancer. The search for invasion into the blood and lymphatic vessels and the assessment of angiogenesis are important aspects of oncological diagnosis. These features determine the prognosis and aggressiveness of the tumor. Traditional manual evaluation methods are time consuming and subject to inter-observer variability. Blood vessel detection is a perfect task for artificial intelligence, which is capable of rapid analyzing thousands of tissue structures in whole slide images.
  • 496
  • 16 Nov 2023
Topic Review
miRNAs Related to Immune Checkpoint Inhibitor Response
The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment of many cancers, although a high number of patients fail to respond to ICIs, which is partially due to the ability of tumor cells to evade immune system surveillance. Non-coding microRNAs (miRNAs) have been shown to modulate the immune evasion of tumor cells, and there is thus growing interest in elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis and treatment response to ICIs. 
  • 495
  • 08 Feb 2024
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