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Topic Review
PTEN in different TME compartments
Mounting preclinical and clinical evidence indicates that rewiring the host immune system in favor of an antitumor microenvironment achieves remarkable clinical efficacy in the treatment of many hematological and solid cancer patients. Nevertheless, despite the promising development of many new and interesting therapeutic strategies, many of these still fail from a clinical point of view, probably due to the lack of prognostic and predictive biomarkers. In that respect, several data shed new light on the role of the tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN) in affecting the composition and function of the tumor microenvironment (TME) as well as resistance/sensitivity to immunotherapy. In this review, we summarize current knowledge on PTEN functions in different TME compartments (immune and stromal cells) and how they can modulate sensitivity/resistance to different immunological manipulations and ultimately influence clinical response to cancer immunotherapy
  • 1.7K
  • 04 Aug 2020
Topic Review
Glioblastoma Organoids
Glioblastoma (GB) is the most lethal primary adult brain tumor. The great number of mutations involved and the aggressiveness of glioblastoma render this type of cancer especially difficult to investigate. Moreover, the lack of reliable GB models, together with its considerable clinical heterogeneity, has impaired a comprehensive investigation of the mechanisms that lead to tumorigenesis, cancer progression, and response to treatments. To address this problem, cerebral organoids have emerged as promising tools to investigate brain biology and to recapitulates the major steps involved in glioblastoma tumorigenesis. Here we exemplify relevant aspects of 3D models of glioblastoma, with a specific focus on organoids and their involvement in basic and translational research.
  • 1.7K
  • 25 Nov 2020
Topic Review
Genetic and Molecular Basis of Von Hippel-Lindau Disease
Von Hippel-Lindau disease (VHL disease or VHL syndrome) is a familial multisystem neoplastic disorder, stemming from germline disease-associated variants of the VHL tumor suppressor gene. VHL protein is involved in oxygen sensing and adaptive response to hypoxia through the EPO-VHL-HIF signaling axis. In recent years, numerous HIF-independent pathways of VHL have been identified, expanding the role of VHL throughout several cellular processes. In addition to VHL syndrome-associated tumors, VHL variations have also been associated with the development of eythrocytosis. Research indicated that there is a distinction between erythrocytosis-causing VHL variations and VHL variations causing VHL disease with tumor development. Therefore, elucidating the molecular background of the pathogenic effects of VHL variants could help determine the best approach to VHL disease management.  
  • 1.7K
  • 24 Mar 2022
Topic Review
Cytokines
Cytokines are key molecules within the tumor microenvironment (TME) that can be used as biomarkers to predict the magnitude of anti-tumor immune responses. During immune monitoring, it has been customary to predict outcomes based on the abundance of a single cytokine, in particular IFN-γ or TGF-β, as a readout of ongoing anti-cancer immunity. However, individual cytokines within the TME can exhibit dual opposing roles. For example, both IFN-γ and TGF-β have been associated with pro- and anti-tumor functions. Moreover, cytokines originating from different cellular sources influence the crosstalk between CD4+ and CD8+ T cells, while the array of cytokines expressed by T cells is also instrumental in defining the mechanisms of action and efficacy of treatments. Thus, it becomes increasingly clear that a reliable readout of ongoing immunity within the TME will have to include more than the measurement of a single cytokine.
  • 1.7K
  • 05 Apr 2021
Topic Review
ACT Therapy for Solid Tumors
Adoptive cell therapy (ACT) with tumor-infiltrating T cells (TILs) has emerged as a promising therapy for the treatment of unresectable or metastatic solid tumors. One challenge to finding a universal anticancer treatment is the heterogeneity present between different tumors as a result of genetic instability associated with tumorigenesis. As the epitome of personalized medicine, TIL-ACT bypasses the issue of intertumoral heterogeneity by utilizing the patient’s existing antitumor immune response. Despite being one of the few therapies capable of inducing durable, complete tumor regression, many patients fail to respond. Recent research has focused on increasing therapeutic efficacy by refining various aspects of the TIL protocol, which includes the isolation, ex vivo expansion, and subsequent infusion of tumor specific lymphocytes.
  • 1.7K
  • 05 May 2021
Topic Review
Myokine Irisin in Cancer
Regular exercise/physical activity is beneficial for the health of an individual and lowers the risk of getting different diseases, including cancer. How exactly exercise results in these health benefits is not known. Recent studies suggest that the molecule irisin released by muscles into the blood stream after exercise may be responsible for these effects.
  • 1.7K
  • 17 Jun 2021
Topic Review
Superficial Spindle Cell Mesenchymal Tumors
Superficial spindle cell mesenchymal tumors form a diverse group of lesions with benign and malignant entities that are often very similar clinically and/or histologically. In children, the patient’s age; the lesion site; the presentation as a mass, nodule, or plaque; and the location in the dermis or subcutis are important features that will guide the dermatologist and the pathologist.
  • 1.7K
  • 02 Oct 2021
Topic Review
Targeting PI3K/Akt/mTOR in AML
Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy, characterized by excessive proliferation and accumulation of immature myeloid blasts in the bone marrow. While reductions of bulk malignant cells can be achieved in the majority of patients by standard chemotherapy consisting of cell cycle active drugs, such as cytarabine and anthracyclines, approximately two-thirds of patients relapse after the induction therapy, highlighting an unmet need for a more targeted therapeutic approach. A rare population of therapy-resistant cells are believed to be the origin of relapse, termed leukemia stem cells (LSCs), also referred to as leukemia-initiating cells (LICs). These cells acquire enhanced self-renewal capacity and exhibit a block in differentiation.
  • 1.7K
  • 23 Sep 2020
Topic Review
Esophageal and Gastric Tumors
Gastric and esophageal tumors are diverse neoplasms that involve mucosal and submucosal tissue layers and include squamous cell carcinomas, adenocarcinomas, spindle cell neoplasms, neuroendocrine tumors, marginal B cell lymphomas, along with less common tumors. The worldwide burden of esophageal and gastric malignancies is significant, with esophageal and gastric cancer representing the ninth and fifth most common cancers, respectively. The approach to diagnosis and staging of these lesions is multimodal and includes a combination of gastrointestinal endoscopy, endoscopic ultrasound, and cross-sectional imaging. Likewise, therapy is multidisciplinary and combines therapeutic endoscopy, surgery, radiotherapy, and systemic chemotherapeutic tools. Future directions for diagnosis of esophageal and gastric malignancies are evolving rapidly and will involve advances in endoscopic and endosonographic techniques including tethered capsules, optical coherence tomography, along with targeted cytologic and serological analyses. 
  • 1.7K
  • 23 Feb 2021
Topic Review
STEAP1–4 and Prostate Cancer
Six-Transmembrane Epithelial Antigen of the Prostate 1–4 (STEAP1–4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. STEAP1–4 can be used as a biomarker and therapeutic target for prostate cancer.
  • 1.7K
  • 24 Aug 2022
Topic Review
Thrombospondin-1 in the Tumor Microenvironment
The identification of thrombospondin-1 as an angiogenesis inhibitor in 1990 prompted interest in its role in cancer biology and potential as a therapeutic target. Decreased thrombospondin-1 mRNA and protein expression are associated with progression in several cancers, while expression by nonmalignant cells in the tumor microenvironment and circulating levels in cancer patients can be elevated. THBS1 is not a tumor suppressor gene, but the regulation of its expression in malignant cells by oncogenes and tumor suppressor genes mediates some of their effects on carcinogenesis, tumor progression, and metastasis. In addition to regulating angiogenesis and perfusion of the tumor vasculature, thrombospondin-1 limits antitumor immunity by CD47-dependent regulation of innate and adaptive immune cells. Conversely, thrombospondin-1 is a component of particles released by immune cells that mediate tumor cell killing. Thrombospondin-1 differentially regulates the sensitivity of malignant and nonmalignant cells to genotoxic stress caused by radiotherapy and chemotherapy. 
  • 1.7K
  • 23 Jun 2021
Topic Review
Genomics-Driven Precision Medicine in Pediatric Solid Tumors
The detection of genomic aberrations in cancers has yielded a wealth of information to discover oncogenic drivers or pathogenic variants that are relevant for the development of precise treatment strategies. Studies have shown promising outcomes in adult cancer patients with well characterized cancer genetic biomarkers.
  • 1.7K
  • 17 Mar 2023
Topic Review
P53
While viewed as the “guardian of the genome”, the importance of the tumor suppressor p53 protein has increasingly gained ever more recognition in modulating additional modes of action related to cell death. Slowly but surely, its importance has evolved from a mutated genetic locus heavily implicated in a wide array of cancer types to modulating lysosomal-mediated cell death either directly or indirectly through the transcriptional regulation of the key signal transduction pathway intermediates involved in this. Taken with its ability to directly modulate mitochondrial outer-membrane permeabilization (and cell death) collectively highlights the complex role that this protein undertakes at the molecular level
  • 1.6K
  • 07 Dec 2020
Topic Review
Colon Fibroblasts and Inflammation
Colorectal cancer (CRC) is the third most common cause of cancer-related death. Patients suffering inflammatory bowel disease have an increased risk of CRC. It is admitted that CRC found its origin within crypts of the colon mucosa, which host the intestinal stem cells (ISCs) responsible of the tissue renewal. ISC behavior is controlled by the fibroblasts that surround the crypt. During inflammation, the signals delivered by fibroblasts are altered, leading to stem cells’ dysregulation, possibly turning them into cancer-initiating cells.
  • 1.6K
  • 23 Jun 2021
Topic Review
Chemo-Immunotherapy in Cancer Treatment
Chemoimmunotherapy is an emerging treatment option for cancer that combines traditional chemotherapy with immunotherapy. This approach aims to increase the efficacy of cancer treatment by simultaneously targeting cancer cells through chemotherapy and boosting the immune system’s ability to fight cancer through immunotherapy.
  • 1.6K
  • 30 May 2023
Topic Review
Group 2 Innate Lymphoid Cells
Group 2 Innate Lymphoid Cells (ILC2s) belong to the family of helper ILCs which provide host defense against infectious agents, participate in inflammatory responses and mediate lymphoid organogenesis and tissue repair, mainly at the skin and mucosal level. Based on their transcriptional, phenotypic and functional profile, ILC2s mirror the features of the adaptive CD4+ Th2 cell subset, both contributing to the so-called type 2 immune response. Similar to other ILCs, ILC2s are rapidly activated by signals deriving from tissue and/or other tissue-resident immune cells. The biologic activity of ILCs needs to be tightly regulated in order to prevent them from contributing to severe inflammation and damage in several organs. Indeed, ILC2s display both enhancing and regulatory roles in several pathophysiological conditions, including tumors.
  • 1.6K
  • 29 Apr 2021
Topic Review
Proteasome Inhibitors
Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literature.
  • 1.6K
  • 18 Apr 2022
Topic Review
Anticancer Activity of Berberine
Berberine is a plant metabolite belonging to the group of isoquinoline alkaloids with strong biological and pharmacological activity. Currently, berberine is receiving considerable interest due to its anticancer activity based on many biochemical pathways, especially its proapoptotic and anti-inflammatory activity. Therefore, the growing number of papers on berberine demands summarizing the knowledge and research trends. The efficacy of berberine in breast and colon cancers seems to be the most promising aspect. Many papers focus on novel therapeutic strategies based on new formulations or search for new active derivatives. The activity of berberine is very important as regards sensitization and support of anticancer therapy in combination with well-known but in some cases inefficient therapeutics. Currently, the compound is being assessed in many important clinical trials and is one of the most promising and intensively examined natural agents.
  • 1.6K
  • 23 Nov 2020
Topic Review
Roles of Copper in Cancer
Copper is an essential element for human life. However, its redox activity can be detrimental for the cell that developed highly coordinated pathways to chelate and traffic copper through the cell or the organism. Owing to its important role in functions essential for cell growth and metabolism, copper concentrations are frequently dysregulated in tumors.
  • 1.6K
  • 05 Jan 2021
Topic Review
Alpha-Ketoglutarate and 5-HMF
Clinical and pre-clinical studies of an anti-tumoral solution containing aKG, 5-HMF, N-acetyl-selenomethionine, and N-acetylmethionine for treating tumors showed, on one hand, good therapeutic efficacy during infusion therapy in prostate cancer patients by increasing the PSA doubling time; on the other hand, a reduction of tumoral mass was shown in lung cancer patients.
  • 1.6K
  • 19 Nov 2021
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