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Topic Review
The KEAP1–NRF2 System
The Kelch-like ECH-associated protein (KEAP1)– Nuclear factor erythroid-derived 2-like 2 (encoded by the Nfe2l2 gene; NRF2) system attracts extensive interest from scientists in basic and clinical cancer research fields, as NRF2 exhibits activity as both an oncogene and tumor suppressor, depending on the context. Especially unique and malignant, NRF2-addicted cancers exhibit high levels of NRF2 expression. Somatic mutations identified in the NRF2 or KEAP1 genes of NRF2-addicted cancers cause the stabilization and accumulation of NRF2. NRF2-addicted cancers hijack the intrinsic roles that NRF2 plays in cytoprotection, including antioxidative and anti-electrophilic responses, as well as metabolic reprogramming, and acquire a marked advantage to survive under severe and limited microenvironments. Therefore, NRF2 inhibitors are expected to have therapeutic effects in patients with NRF2-addicted cancers. In contrast, NRF2 activation in host immune cells exerts significant suppression of cancer cell growth, indicating that NRF2 inducers also have the potential to be therapeutics for cancers. Thus, the KEAP1–NRF2 system makes a broad range of contributions to both cancer development and suppression. These observations thus demonstrate that both NRF2 inhibitors and inducers are useful for the treatment of cancers with high NRF2 activity.
  • 1.2K
  • 12 Jan 2021
Topic Review
PET for Microenvironment-Targeted Therapy
 Quantitative parameters of FDG-PET, such as SUV and TLG have been used to evaluate therapeutic response. Recent advancement in anti-cancer therapeutics showed that tumor response to molecular-targeted drugs and immune-checkpoint inhibitors is different from conventional chemotherapy in terms of temporal metabolic alteration and morphological change after the course of effective therapy. Metabolic changes and temporal enlargement due to immune cell infiltration seen after immune-checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies facilitated the modification of conventional Response Evaluation Criteria in Solid Tumor and FDG-PET response evaluation criteria. Tumor microenvironment including cancer stem cells (CSCs) that is thought to be a root cause of tumor heterogeneity; is considered a target of novel and effective therapy.   Accumulation of FDG reflects glucose metabolism of both cancer cells and immunologically competent cells in the tumor microenvironment. Immunological reaction to the therapy differs among patients according to the individual immune function. Considering the heterogeneity of tumor tissue and individual variation in tumor response to immunotherapy, radiomics approach combines quantitative image features with deep learning algorithm have the potentials to improve response assessment in more personalized treatment.   Stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-targeted α-particle therapy has been introduced, because SDF-1/CXCR4 axis is known to increase epithelial-mesenchymal transition to facilitate invasion and metastasis, and regulate immune response by accelerating T cell proliferation as well as PD-1 and PD-L1 expression in cancer cells and cytotoxic T lymphocytes, respectively. Prominent energy profile and biological effect of α-particles are promising as an alternative in targeted radionuclide therapy (TRT). Radiation dosimetry according to the theranostics approach will permit accurate TRT and artificial intelligence-based treatment decision making and precise response evaluation would be a precision nuclear medicine in the future.
  • 1.2K
  • 09 Feb 2021
Topic Review
Plant Extracts for Cachexia
A natural product is a chemical compound or substance produced by a living organism—that is, found in nature. Sequela is a result or condition that follows from a disease or illness Cachexia is a condition that causes extreme weight loss and muscle wasting. It is a symptom of many chronic conditions, such as cancer, chronic renal failure, HIV, and multiple sclerosis.
  • 1.2K
  • 16 Sep 2020
Topic Review
Epithelial–Mesenchymal Transition & prostate cancer
Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However this multifaceted process is also implicated in cancer progression and metastasis in many tumors, including prostate cancer. Moreover, recent evidence suggests that EMT-induced cell plasticity is involved in the development of therapy resistance in prostate cancer cells.
  • 1.2K
  • 02 Jul 2021
Topic Review
Reactive Oxygen Species in Acute Lymphoblastic Leukaemia
Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children and adolescents. Approximately 70% of patients survive >5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers and are emerging as significant contributors to the leukaemogenesis of ALL. ROS modulate the function of signalling proteins through oxidation of cysteine residues, as well as promote genomic instability by damaging DNA, to promote chemotherapy resistance. Current therapeutic approaches exploit the pro-oxidant intracellular environment of malignant B and T lymphoblasts to cause irreversible DNA damage and cell death, however these strategies impact normal haematopoiesis and lead to long lasting side-effects. Therapies suppressing ROS production, especially those targeting ROS producing enzymes such as the NADPH oxidases (NOXs), are emerging alternatives to treat cancers and may be exploited to improve the ALL treatment. 
  • 1.2K
  • 02 Apr 2022
Topic Review
Patient-Derived Cancer Organoids
The emergence of three-dimensional human organoids has opened the door for the development of patient-derived cancer organoid (PDO) models, which closely recapitulate parental tumor tissue. 
  • 1.2K
  • 01 Jun 2021
Topic Review
Transcriptional Spatial Profiling
Transcriptional spatial profiling enables characterization of the cancer immune profile by providing quantitative gene expression data that retains critical spatial information. It encompasses both well-known technologies such as in-situ hybridization and digital spatial profiling as well as emerging technologies such as Visium Spatial Gene Expression Solution. These technologies may be used to identify and subsequently block the source of tumour heterogeneity that underlies treatment resistance, disease progression and cancer relapse. By combining sequencing data with spatial information, transcriptional spatial profiling technologies hold great promise in uncovering novel biomarkers, potential drug targets and pathogenic mechanisms. 
  • 1.2K
  • 22 Sep 2020
Topic Review
Somatostatin-Dopamine Chimeric Compounds
The growing knowledge of receptor profile expression in Neuroendocrine neoplasms (NENs) has led to synthesis of several chimeric molecules targeting multi-receptors, with a particular interest for SSTs and DRs due to the functional interactions between these receptors. On these assumptions, novel chimeric compounds, embracing somatostatin and dopamine features, were developed opening new routes for NENs treatments.
  • 1.2K
  • 18 Feb 2021
Topic Review
Mitochondria Exchanges within the tumor
In this review, we focus on how CAFs participate in cancer progression by modulating cancer cells metabolic functions and mitochondrial apoptosis.Resistance of solid cancer cells to chemotherapies and targeted therapies is not only due to the mutational status of cancer cells but also to the concurring of stromal cells of the tumor ecosystem, such as immune cells, vasculature and cancer-associated fibroblasts (CAFs). The reciprocal education of cancer cells and CAFs favors tumor growth, survival and invasion. Mitochondrial function control, including the regulation of mitochondrial metabolism, oxidative stress and apoptotic stress are crucial for these different tumor progression steps. In this review, we focus on how CAFs participate in cancer progression by modulating cancer cells metabolic functions and mitochondrial apoptosis.
  • 1.2K
  • 27 Oct 2020
Topic Review
“Omics” Biomarkers in Pancreatic Cancer
Pancreatic cancer is one of the most fatal malignancies and the seventh leading cause of cancer-related deaths related to late diagnosis, poor survival rates, and high incidence of metastasis. 
  • 1.2K
  • 18 May 2021
Topic Review
Three-Dimensional Culture Systems
It is getting more and more clear that cancer cell culture models are switching from two-dimension to three-dimensional, in order to better reflect in vivo situations where tumor cells have to cope with a highly interactive three-dimensional microenvironment. Several such culture models have been reported, predominantly multicellular tumor spheroids (MCTS) and patient-derived tumor organoids (PDTO). These are used both to investigate fundamental aspects of cancer development and as test systems for innovative therapies against gastric cancer, the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The authors review the actual state of research in this field to provide an overview of the contribution of MCTS and PDTO, especially in the areas of molecular profiling, drug discovery, pathogen infection, and personalized medicine.
  • 1.2K
  • 18 Feb 2021
Topic Review
3D Lung Cancer Models
3D models of cancer primarily refer to patient-derived xenografts, spheroids, and organoids and have been established for a variety of cancer types, including lung cancer. 3D lung cancer models have been demonstrated to more accurately model patient cancers and have the potential to advance basic, translational, and clinical studies.
  • 1.2K
  • 13 Apr 2021
Topic Review
Representative Drivers for TB Development and p-EMT Induction
Tumor budding (TB), a microscopic finding in the stroma ahead of the invasive fronts of tumors, has been well investigated and reported as a prognostic marker in head and neck squamous cell carcinoma (HNSCC). Epithelial–mesenchymal transition (EMT) is a crucial step in tumor progression and metastasis, and its status cannot be distinguished from TB. The current understanding of partial EMT (p-EMT), the so-called halfway step of EMT, focuses on the tumor microenvironment (TME). Although this evidence has been investigated, the clinicopathological and biological relationship between TB and p-EMT remains debatable. At the invasion front, previous research suggested that cancer-associated fibroblasts (CAFs) are important for tumor progression, metastasis, p-EMT, and TB formation in the TME. 
  • 1.2K
  • 21 Feb 2023
Topic Review
Tumour Immune Microenvironment
Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. In this entry, we focus on the metabolic dysregulation exerted by tumour cells on the immune microenvironment, leading to tumour immunosuppression. This metabolic rewiring and crosstalk with the tumour microenvironment also play a key role in cell proliferation, metastasis, and the development of treatment resistance. Nonetheless, greater understanding of the metabolic crosstalk presents strategies that aid in the precision targeting of altered tumour metabolism, including therapeutic strategies combining metabolic inhibition with immunotherapy.
  • 1.2K
  • 09 Dec 2020
Topic Review
Cell-Free DNA
Cell-free DNA (cfDNA) testing, is an emerging “liquid biopsy” tool for noninvasive lymphoma detection, and an increased amount of data are now available to use this technique with accuracy, especially in classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). The advantages of cfDNA include simplicity of repeated blood sample acquisition over time; dynamic, noninvasive, and quantitative analysis; fast turnover time; reasonable cost; and established consistency with results from tumor genomic DNA. cfDNA analysis offers an easy method for genotyping the overall molecular landscape of pediatric and adult cHL and may help in cases of diagnostic difficulties between cHL and other lymphomas.
  • 1.2K
  • 10 Mar 2021
Topic Review
PRDM12 in Health and Diseases
PRDM12 is a member of the PRDI-BF1 (positive regulatory domain I-binding factor 1) homologous domain (PRDM)-containing protein family, a subfamily of Kruppel-like zinc finger proteins, controlling key processes in the development of cancer. PRDM12 is expressed in a spatio-temporal manner in neuronal systems where it exerts multiple functions. PRDM12 is essential for the neurogenesis initiation and activation of a cascade of downstream pro-neuronal transcription factors in the nociceptive lineage.
  • 1.2K
  • 12 Nov 2021
Topic Review
Liquid Biopsy for Ophthalmic Malignancies
Intraocular solid malignancy biopsy is usually not performed due to the risk and fear of extraocular extension. Recently, liquid biopsy has gained in popularity in this field. Liquid biopsy allows the diagnosis of intraocular malignancies as well as its monitoring in retinoblastoma. Liquid biopsy may help the clinican to better understand the metastatic spread, especially in uveal melanoma.
  • 1.2K
  • 22 Sep 2021
Topic Review
Tunneling Nanotubes for Glioblastoma Treatment
Communication between cells helps tumors acquire resistance to chemotherapy and makes the struggle against cancer more challenging. Tunneling nanotubes (TNTs) are long channels able to connect both nearby and distant cells, contributing to a more malignant phenotype. This finding might be useful in designing novel strategies of drug delivery exploiting these systems of connection. This would be particularly important to reach tumor niches, where glioblastoma stem cells proliferate and provoke immune escape, thereby increasing metastatic potential and tumor recurrence a few months after surgical resection of the primary mass. Along with the direct inhibition of TNT formation, TNT analysis, and targeting strategies might be useful in providing innovative tools for the treatment of this tumor.
  • 1.2K
  • 29 Mar 2022
Topic Review
Connexins and Integrins in Exosomes
Connexins and integrins, the two structurally and functionally distinct families of transmembrane proteins, have been shown to be inter-connected by various modes of cross-talk in cells, such as direct physical coupling via lateral contact, indirect physical coupling via actin and actin-binding proteins, and functional coupling via signaling cascades.
  • 1.2K
  • 11 Oct 2021
Topic Review
Targeting Tryptophan Metabolism to Treat Cancers
Major hallmarks of cancers are connected to dysfunctions in many metabolic pathways aiming at providing the energetic needs and the raw material for cellular growth and the signaling molecules needed for oncogenesis. Tryptophan (TRP) catabolism through the kynurenine (KYN) pathway was reported to play immunosuppressive actions across many types of cancer. However, results from clinical trials assessing the benefit of inhibiting key limiting enzymes of this pathway such as indoleamine 2,3-dioxygenase (IDO1) or tryptophan 2,3-dioxygenase (TDO2) failed to meet the expectations. Bearing in mind the complexity of the tumoral terrain and the existence of different cancers with IDO1/TDO2 expressing and non-expressing tumoral cells, here we present a comprehensive analysis of the TRP global metabolic hub and the approach of inhibiting these pathways as a potential therapeutic option to treat cancers such as liver cancers. 
  • 1.2K
  • 29 Mar 2022
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