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Topic Review
Forkhead Box Proteins in AML
Forkhead box (FOX) proteins are a group of transcriptional factors implicated in different cellular functions such as differentiation, proliferation and senescence. A growing number of studies have focused on the relationship between FOX proteins and cancers, particularly hematological neoplasms such as acute myeloid leukemia (AML). FOX proteins are widely involved in AML biology, including leukemogenesis, relapse and drug sensitivity. Here we explore the role of FOX transcription factors in the major AML entities, according to “The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia”, and in the context of the most recurrent gene mutations identified in this heterogeneous disease.
  • 759
  • 22 Sep 2021
Topic Review
Cancer Stem Cells in Ovarian Cancer
Ovarian cancer is the most lethal neoplasm of the female genital organs. Despite indisputable progress in the treatment of ovarian cancer, the problems of chemo-resistance and recurrent disease are the main obstacles for successful therapy. One of the main reasons for this is the presence of a specific cell population of cancer stem cells.
  • 759
  • 03 Mar 2022
Topic Review
Immune Evasion in Ewing Sarcoma and Osteosarcoma
Immunogenicity of the tumor environment can be enhanced by altering macrophage differentiation and polarization or by administering activating cytokines. Additional tumor microenvironment-directed approaches could be designed to interfere with the immunosuppressive mechanisms active in the immunological deserts, e.g., blocking immunosuppressive extracellular vesicles (EVs) or immunosuppressive metabolic mechanisms, or probably both. This can be achieved by engineering bifunctional TCR or CAR transgenic T cells that could simultaneously manipulate the tumor microenvironment (TME) and target tumor-specific cell surface antigens. Moreover, epigenetic activation of gene expression from non-coding sequences may provide targetable neo-epitopes even in immune inert malignancies.
  • 759
  • 13 Jan 2023
Topic Review
Mechanisms of Polyphenols as Treatment Against Neuroblastoma
Neuroblastoma (NB) is an extracranial tumor of the peripheral nervous system arising from neural crest cells. It is the most common malignancy in infants and the most common extracranial solid tumor in children. The treatment for high-risk NB involves chemotherapy and surgical resection followed by high-dose chemotherapy with autologous stem-cell rescue and radiation treatment. However, those with high-risk NB are susceptible to relapse and the long-term side effects of standard chemotherapy. Polyphenols, including the sub-class of flavonoids, contain more than one aromatic ring with hydroxyl groups.
  • 759
  • 06 Apr 2023
Topic Review
Kaposi Sarcoma
Kaposi’s sarcoma is an angioproliferative neoplasm that typically occurs in the lower limbs and can enter into differential diagnosis with several other rarer skin diseases. The principal differential diagnosis concerns primary cutaneous lymphomas, of which mycosis fungoides represent the most frequent primary cutaneous T-cell lymphoma. Other rare forms include primary cutaneous B-cell lymphomas, which can be divided into indolent and aggressive forms, such as the primary cutaneous diffuse large B-cell lymphoma, leg type, and lymphomatoid papulomatosis (LyP). In the case of indolent lesions, skin-directed therapies, limited-field radiotherapy, and surgical approaches can be good options. At the same time, different management, with systemic chemotherapy and allogenic bone marrow transplant, is required with aggressive neoplasms, such as blastic plasmacytoid dendritic cell neoplasia or advanced mycosis fungoides. The dermatologist’s role can be crucial in recognizing such diseases and avoiding misdiagnosis, giving the pathologist the correct clinical information for an accurate diagnosis, and starting the suitable therapy.
  • 759
  • 10 May 2023
Topic Review
MiRNA with impact on ZEB family in Glioma
Epithelial to mesenchymal transition (EMT) is a complex, molecular program that plays an essential part in the progression of epithelial tumours to invasive phenotypes. However, gliomas do not engage in a typical EMT pathway, as these tumours do not originate from classical epithelial tissue. Nevertheless, EMT-like changes, which are the main cause of increased invasiveness, stem cell signature and loss of cell–cell contact, can contribute extensively to increased progression and metastasis also in non-epithelial tumours, including gliomas. Accordingly, EMT-promoting transcription factors (EMT-TFs), such as Snail (SNAI1), Slug (SNAI2), Twist1 and Twist2 appear to play pivotal roles in various aspects of tumourigenic processes. Among them, ZEB family members, such as ZEB1 and ZEB2, i.e., zinc finger E-box binding homeobox proteins, are also important modulators of the molecular network in gliomas with a substantial impact on the proliferation, invasion and migration of tumourigenic cells.
  • 759
  • 17 May 2023
Topic Review
Immunotherapy during the Immediate Perioperative Period
Tumor excision is a necessary life-saving procedure in most solid cancers. However, surgery and the days before and following it, known as the immediate perioperative period (IPP), entail numerous prometastatic processes, including the suppression of antimetastatic immunity and direct stimulation of minimal residual disease (MRD). Thus, the IPP is pivotal in determining long-term cancer outcomes, presenting a short window of opportunity to circumvent perioperative risk factors by employing several therapeutic approaches, including immunotherapy. Nevertheless, immunotherapy is rarely examined or implemented during this short timeframe, due to both established and hypothetical contraindications to surgery. This entry summarizes existing and potential immuno-theraputic approaches to exploit the immediate perioperative period to prevent future metastatic disease.
  • 759
  • 23 Aug 2023
Topic Review
Cancer-Associated Fibroblasts and T Cells
CAFs release a number of different factors, including chemokines, cytokines, and growth factors, that promote immunosuppression through recruitment of immunosuppressive cells such as T regulatory cells (Tregs) and myeloid cells, upregulation of immune checkpoint molecules on T cells, and regulation of T-cell migration.
  • 758
  • 30 Jun 2021
Topic Review
Treatment Strategies for KRAS-Mutated Non-Small-Cell Lung Cancer
Activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS) are highly prevalent in solid tumours and are frequently found in 35% of lung, 45% of colorectal, and up to 90% of pancreatic cancers. Mutated KRAS is a prognostic factor for disease-free survival (DFS) and overall survival (OS) in NSCLC and is associated with a more aggressive clinical phenotype, highlighting the need for KRAS-targeted therapy. Once considered undruggable due to its smooth shallow surface, a breakthrough showed that the activated G12C-mutated KRAS isozyme can be directly inhibited via a newly identified switch II pocket. This discovery led to the development of a new class of selective small-molecule inhibitors against the KRAS G12C isoform. Sotorasib and adagrasib are approved in locally advanced or metastatic NSCLC patients who have received at least one prior systemic therapy. 
  • 758
  • 28 Mar 2023
Topic Review
Hyperoxia Effects in Cancer
Hyperoxia effects on cancer biology were explored following multiple pathways, using both in vitro cancer cell cultures and in vivo tumoral animal models. Experimental data support clinical evidences demonstrating that hyperoxia, mainly if prolonged, can induce lung injury and cerebral damage, and this can be counteracted by down-modulation of Akt, by low-dose vitamin D or aspirin.
  • 757
  • 10 Dec 2021
Topic Review
Exosomes in Pancreatic Cancer
Multiple lines of evidence have showed that exosomes are actively involved in intercellular communication by transferring their cargos of bioactive molecules to recipient cells within the tumor microenvironment and systemically. Intriguingly, exosomes may exert both protumor and antitumor effects, supporting or hampering processes that play a role in the pathogenesis and progression of PC, including shifts in tumor metabolism, proliferation, invasion, metastasis, and chemoresistance. They also have a dual role in PC immunomodulation, exerting immunosuppressive or immune enhancement effects through several mechanisms. PC-derived exosomes also induce systemic metabolic alterations, leading to the onset of diabetes and weight loss. Moreover, exosomes have been described as promising diagnostic and prognostic biomarkers for PC. Their potential application in PC therapy as drug carriers and therapeutic targets is under investigation.
  • 756
  • 13 Apr 2021
Topic Review
Optic Pathway Glioma
Type 1 neurofibromatosis (NF1) is a dominantly inherited condition predisposing to tumor development. Optic pathway glioma (OPG) is the most frequent central nervous system tumor in children with NF1, affecting approximately 15–20% of patients. The lack of well-established prognostic markers and the wide clinical variability with respect to tumor progression and visual outcome make the clinical management of these tumors challenging, with significant differences among distinct centers. We reviewed published articles on OPG diagnostic protocol, follow-up and treatment in NF1. Cohorts of NF1 children with OPG reported in the literature and patients prospectively collected in our center were analyzed with regard to clinical data, tumor anatomical site, diagnostic workflow, treatment and outcome.
  • 756
  • 01 Sep 2021
Topic Review
Paraneoplastic Syndromes in Patients with Keratinocyte Skin Cancer
A variety of well-characterized cutaneous paraneoplastic syndromes (PNS) are diagnosed during internal malignancies; however, the spectrum of keratinocyte skin neoplasms (KSC) related to PNS is still obscure. Aim of the present research synthesis was to provide a typology of the spectrum of these PNS based on a focused literature search.
  • 756
  • 12 Jan 2022
Topic Review
Next-Generation Target for Cancer Immunotherapy
The most successful strategies for solid cancer immunotherapy have centered on targeting the co-stimulatory and co-inhibitory T cell molecules that regulate T cell activation. Although immunotherapy that targets surface receptors such as CTLA-4 and/or PD-1 with recombinant antibodies has been a game changer for cancer treatment, a sizeable subset of patients still fail to respond to, and even fewer patients are cured by, these therapy regimens. The identification of alternate and potentially additive immune checkpoint candidates is intended to improve immunotherapies for a large number of cancer patients. Therefore, we focused on checkpoints located inside immune cells as suitable targets for future cancer drugs. We demonstrated, in recent years, the crucial T lymphocyte-intrinsic role of the orphan nuclear receptor NR2F6 as an intracellular checkpoint in fine-tuning adaptive immunity. NR2F6 induced an anti-inflammatory signal in the T cell compartment.
  • 755
  • 23 Jun 2021
Topic Review
Arginine Metabolism in Oral Tongue Squamous Cell Carcinoma
Arginine is a semi-essential amino acid with a complex metabolism pathway and diverse functionality, which spans well beyond its role in the immune system. Cancers that are ‘arginine auxotrophic’ rely on extracellular arginine as a crucial substrate for proliferation and growth. Capitalizing on this vulnerability, there are numerous clinical trials evaluating the therapeutic benefits of depleting arginine in multiple types of cancer, including those occurring in the head and neck. However, head and neck cancers are different and are nonauxotrophic for arginine. Here, researchers explored the intricacies of arginine metabolism in tongue cancer in order to better understand the therapeutic potential of this biological vulnerability. 
  • 755
  • 13 Dec 2021
Topic Review
Clinical Applications of the Microbiome in Oral Mucositis
Oral mucositis (OM) is a common and impactful toxicity of standard cancer therapy, affecting up to 80% of patients. Its aetiology centres on the initial destruction of epithelial cells and the increase in inflammatory signals. These changes in the oral mucosa create a hostile environment for resident microbes, with oral infections co-occurring with OM, especially at sites of ulceration. However, increasing evidence suggests that oral microbiome changes occur beyond opportunistic infection, with a growing appreciation for the potential role of the microbiome in OM development and severity.
  • 755
  • 19 May 2023
Topic Review
Genomically-Guided Precision Radiation Treatment
Genetic information is seldom incorporated in formulating radiation treatment recommendations for patients with cancer, even though genetic information is now well established to be prognostic and predictive of cancer outcomes and response to systemic therapy. With the increasing accessibility to and use of genetic testing, tumor, and germline genetic data have the potential to inform clinical decisions by improving the efficacy of radiation treatment and ensuring the safety of treatment delivery.
  • 755
  • 20 Nov 2023
Topic Review
Microbiome in Cancer Development and Treatment
Targeting the microbiome, microbiota-derived metabolites, and related pathways represents a significant challenge in oncology. Microbiome analyses have confirmed the negative impact of cancer treatment on gut homeostasis, resulting in acute dysbiosis and severe complications, including massive inflammatory immune response, mucosal barrier disruption, and bacterial translocation across the gut epithelium. Moreover, recent studies revealed the relationship between an imbalance in the gut microbiome and treatment-related toxicity. Recently, microbiota modulation via probiotic supplementation and fecal microbiota transplantation represents a new trend in cancer patient care, aiming to increase bacterial diversity, alleviate acute and long-term treatment-induced toxicity, and improve the response to various treatment modalities. A more detailed understanding of the complex relationship between the microbiome and host can significantly contribute to integrating a microbiome-based approach into clinical practice. 
  • 755
  • 08 Apr 2024
Topic Review
HRQOL in Oral Cancer Patients
The scope of the present entry was to highlight possible sources of bias that could be encountered when evaluating HRQOL (Health-Related Quality of Life) in patients treated for oral cancer. The second aim was to lay the foundation of a standardized protocol for cohort selection, data collection, and stratification that could enhance knowledge in the field.
  • 754
  • 22 Sep 2021
Topic Review
Thrombosis and Immune Checkpoint Inhibitors
Thromboembolism is a common complication in patients with cancer and is associated with significant morbidity and mortality. Anticancer treatment is a known risk factor of cancer-associated thrombosis. Immune checkpoint inhibitors have become a mainstay of treatment in various cancers. Both venous and arterial thrombosis have been increasingly reported as adverse events associated with immune checkpoint inhibitors in recent studies, with a cumulative incidence of venous thrombosis to be 5–8% at 6 months and over 10% at 12 months. Additionally, rates of approximately 1–5% for arterial thrombosis were reported at 12 months. Data also showed an association of thromboembolism with adverse survival. Many pertinent clinical questions in this population deserve further investigation, including the risks of thrombosis associated with immune checkpoint inhibitors as compared to those with traditional systemic therapy, associated risk factors, and the optimal prevention and treatment strategies.
  • 754
  • 24 Sep 2021
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