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Topic Review
Triple-Negative Breast Cancer
Triple negative breast cancer (TNBC) is a heterogeneous tumor characterized by early recurrence, high invasion, and poor prognosis. Currently, its treatment includes chemotherapy, which shows a suboptimal efficacy. However, with the increasing studies on TNBC subtypes and tumor molecular biology, great progress has been made in targeted therapy for TNBC. The new developments in the treatment of breast cancer include targeted therapy, which has the advantages of accurate positioning, high efficiency, and low toxicity, as compared to surgery, radiotherapy, and chemotherapy. Given its importance as cancer treatment, we review the latest research on the subtypes of TNBC and relevant targeted therapies. 
  • 571
  • 30 Jun 2021
Topic Review
Breast Cancer-Associated Fibroblasts
Breast cancer-associated fibroblasts (BCAFs) are the CAFs present in breast cancers with genetic and phenotypic characteristics similar to CAFs. CAFs originate from a diverse range of cells, including endothelial cells, adipocytes, pericytes, and MSCs. Although CAFs were derived from endothelial cells and pericytes, the derivation was not tested in breast cancer models similar to other cancers. BCAFs have also been derived from adipocytes that lead to a desmoplastic microenvironment. BCAFs can originate from MSCs, which contribute to angiogenesis through up-regulation of clusterin leading to tumorigenesis. BCAFs possess the fibrillar collagen receptor, DDR2, which rearranges collagen fibers to develop an invasive and metastatic TME. Additionally, integrin α11 in BCAFs interacts with platelet-derived growth factor receptor beta (PDGFRβ) and promotes invasiveness by activating c-Jun N-terminal kinase (JNK) and producing a matricellular protein, tenascin C.
  • 571
  • 14 Jan 2022
Topic Review
A Nanoparticle’s Journey to the Tumor
Nanomedicines represent the cutting edge of today’s cancer therapeutics. Seminal research decades ago has begun to pay dividends in the clinic, allowing for the delivery of cancer drugs with enhanced systemic circulation while also minimizing off-target toxicity. Despite the advantages of delivering cancer drugs using nanoparticles, micelles, or other nanostructures, only a small fraction of the injected dose reaches the tumor, creating a narrow therapeutic window for an otherwise potent drug. First-pass metabolism of nanoparticles by the reticuloendothelial system (RES) has been identified as a major culprit for the depletion of nanoparticles in circulation before they reach the tumor site. To overcome this, new strategies, materials, and functionalization with stealth polymers have been developed to improve nanoparticle circulation and uptake at the tumor site. 
  • 571
  • 14 Apr 2022
Topic Review
High-Grade Serous Ovarian Cancer
High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients (BRCA germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy. Therefore, there is an urgent need to identify the substantial risk factors for both predisposed and low-risk populations of women, as well as to create an economically and clinically justified screening program. 
  • 571
  • 14 Feb 2024
Topic Review
STAT6
Inflammation is the main driver of tumor initiation and progression in colitis-associated colorectal cancer (CAC). Recent findings have indicated that the signal transducer and activator of transcription 6 (STAT6) plays a fundamental role in the early stages of CAC, and STAT6 knockout (STAT6−/−) mice are highly resistant to CAC development. Regulatory T (Treg) cells play a major role in coordinating immunomodulation in cancer; however, the role of STAT6 in the induction and function of Treg cells is poorly understood. To clarify the contribution of STAT6 to CAC, STAT6−/− and wild type (WT) mice were subjected to an AOM/DSS regimen, and the frequency of peripheral and local Treg cells was determined during the progression of CAC. When STAT6 was lacking, a remarkable reduction in tumor growth was observed, which was associated with decreased inflammation and an increased number of CD4+CD25+Foxp3+ cells. STAT6 has a direct role in the induction and function of Treg cells during CAC development.  
  • 570
  • 22 Sep 2021
Topic Review
NETs in Cancer
Neutrophils constitute the first line of defense against foreign invaders using major effector mechanisms: phagocytosis, degranulation, and neutrophil extracellular traps (NETs) formation. NETs are composed from decondensed nuclear or mitochondrial DNA decorated with proteases and various inflammatory mediators. Cancer cells recruit neutrophils (tumor-associated neutrophils, TANs), releasing NETs to the tumor microenvironment. NETs were found in various samples of human and animal tumors. The role of the NETs in tumor development increasingly includes cancer immunoediting and interactions between the immune system and cancer cells. According to the accumulated evidence, NETs awake dormant cancer cells, causing tumor relapse, as well as its unconstrained growth and spread. NETs play a key regulatory role in the tumor microenvironment, such as the development of distant metastases through the secretion of proteases, i.e., matrix metalloproteinases and proinflammatory cytokines. NETs, furthermore, directly exacerbate tumor aggressiveness by enhancing cancer migration and invasion capacity.
  • 569
  • 24 Sep 2021
Topic Review
MET in Non-Small-Cell Lung Cancer
Non-Small-Cell Lung Cancer (NSCLC) can harbour different MET alterations, such as MET overexpression (MET OE), MET gene amplification (MET AMP), or MET gene mutations. Retrospective studies of surgical series of patients with MET-dysregulated NSCLC have shown worse clinical outcomes irrespective of the type of specific MET gene alteration. On the other hand, earlier attempts failed to identify the ‘druggable’ molecular gene driver until the discovery of MET exon 14 skipping mutations (METex14). METex14 are rare and amount to around 3% of all NSCLCs. Patients with METex14 NSCLC attain modest results when they are treated with immune checkpoint inhibitors (ICIs). New selective MET inhibitors (MET-Is) showed a long-lasting clinical benefit in patients with METex14 NSCLC and modest activity in patients with MET AMP NSCLC. 
  • 569
  • 19 Oct 2023
Topic Review
Chromosomal Instability in AML
Chromosome instability (CIN) is an increased rate where chromosome acquire alterations due to errors in cell division. CIN creates genetic and cytogenetic diversity and is a common feature in hematological malignancies such as acute myeloid leukemia (AML). Low to moderate levels of CIN seems to be well tolerated and can promote cancer proliferation, genetic diversity, and tumor evolution. However, high levels of CIN seems to be lethal, where enhancing CIN could improve AML treatment. However, little is known about CIN in AML.
  • 568
  • 16 Jun 2021
Topic Review
Cervical Cancer
Cervical cancer is one of the most common malignancies in women worldwide and its management remains challenging and complex. As Cytochrome4Z1 (CYP4Z1) is overexpressed in many tumours, its expression in cervical cancer is unknown. Therefore, the present study aimed to evaluate CYP4Z1 expression in cervical cancers. Methods: CYP4Z1 expression was immunohistochemically assessed in 100 cases of cervical cancers along with ten normal cervix tissues, and the enzyme’s relationship to several clinicopathological features and survival was explored. Results: CYP4Z1 was strongly expressed in 55% of cervical cancer patients. Normal cervix samples were negative for CYP4Z1 expression. Importantly, this expression was significantly found in patients with the late stage of the disease, lymph node metastasis, and high tumour invasion (p < 0.05). Interestingly, CYP4Z1 expression was significantly correlated with shorter survival times of cervical cancer patients. Univariate analysis showed that CYP4Z1 expression, tumour stage, lymph node metastasis, and tumour invasion were significantly correlated with patient survival (p < 0.05). The multivariate analysis revealed that only CYP4Z1 expression and tumour stage were significantly correlated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is associated with cervical cancer patients’ survival and may serve as an independent predictor of poor prognosis in cervical cancer patients. 
  • 568
  • 22 Sep 2021
Topic Review
Metabolism-Associated Epigenetic and Immunoepigenetic Re-programming in Liver Cancer
Metabolic reprogramming and epigenetic changes have been characterized as hallmarks of liver cancer. Metabolic intermediates serve as crucial substrates for various epigenetic modulations, from post-translational modification of histones to DNA methylation. In turn, epigenetic changes can alter the expression of metabolic genes supporting on the one hand, the increased energetic demand of cancer cells and, on the other hand, influence the activity of tumor-associated immune cell populations. In this review, we will illustrate the most recent findings about metabolic reprogramming in liver cancer. We will focus on the metabolic changes characterizing the tumor microenvironment and on how these alterations impact on epigenetic mechanisms involved in the malignant progression. Furthermore, we will report our current knowledge about the influence of cancer-specific metabolites on epigenetic reprogramming of immune cells. Finally, we will review the current strategies to target metabolic and epigenetic pathways and their therapeutic potential in liver cancer, alone or in combinatorial approaches.
  • 568
  • 13 Dec 2021
Topic Review
Role microRNA in Prostate and Breast Cancer
Micro ribonucleic acids (microRNAs or miRNAs) form a distinct subtype of non-coding RNA and are widely recognized as one of the most significant gene expression regulators in mammalian cells. Mechanistically, the regulation occurs through microRNA binding with its response elements in the 3’-untranslated region of target messenger RNAs (mRNAs), resulting in the post-transcriptional silencing of genes, expressing target mRNAs. Compared to small interfering RNAs, microRNAs have more complex regulatory patterns, making them suitable for fine-tuning gene expressions in different tissues. Dysregulation of microRNAs is well known as one of the causative factors in malignant cell growth. Breast cancer (BCa) is the most common cancer in women worldwide and seriously impairs patients’ physical health. Its incidence has been predicted to rise further. Mounting evidence indicates that microRNAs play key roles in tumorigenesis and development. Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men. Different microRNAs play an important role in PCa. Early diagnosis of BCa and PCa using microRNAs is very useful for improving individual outcomes in the framework of predictive, preventive, and personalized (3P) medicine, thereby reducing the economic burden.
  • 568
  • 03 Feb 2023
Topic Review
Gold Nanoparticles for Cancer Theragnosis
Research on cancer theragnosis with gold nanoparticles (AuNPs) has rapidly increased, as AuNPs have many useful characteristics for various biomedical applications, such as biocompatibility, tunable optical properties, enhanced permeability and retention (EPR), localized surface plasmon resonance (LSPR), photothermal properties, and surface enhanced Raman scattering (SERS). AuNPs have been widely utilized in cancer theragnosis, including phototherapy and photoimaging, owing to their enhanced solubility, stability, biofunctionality, cancer targetability, and biocompatibility.
  • 567
  • 02 Nov 2020
Topic Review
Extracellular Vesicles in Pancreatic Cancer
Pancreatic cancer (PC) is among the most devastating digestive tract cancers worldwide. This cancer is characterized by poor diagnostic detection, lack of therapy, and difficulty in predicting tumorigenesis progression. In recent years, the attention of many researchers has been concentrated on the role of extracellular vesicles and of a particular subset of extracellular vesicles, known as exosomes. These nanovesicles are able to deliver their cargos to recipient cells playing key roles in the pathogenesis and progression of many pancreatic precancerous conditions. 
  • 567
  • 29 Jun 2021
Topic Review
Natural Killer Cells/Dendritic Cells
Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer that accounts for almost 85% of lung cancer cases worldwide. Although recent advances in chemotherapy, radiotherapy, and immunotherapy have helped in the clinical management of these patients, the survival rate in advanced stages remains dismal. Furthermore, there is a critical lack of accurate prognostic and stratification markers for emerging immunotherapies. To harness immune response modalities for therapeutic benefits, a detailed understanding of the immune cells in the complex tumor microenvironment (TME) is required. Among the diverse immune cells, natural killer (NK cells) and dendritic cells (DCs) have generated tremendous interest in the scientific community. NK cells play a critical role in tumor immunosurveillance by directly killing malignant cells. DCs link innate and adaptive immune systems by cross-presenting the antigens to T cells. The presence of an immunosuppressive milieu in tumors can lead to inactivation and poor functioning of NK cells and DCs, which results in an adverse outcome for many cancer patients, including those with NSCLC. Recently, clinical intervention using modified NK cells and DCs have shown encouraging response in advanced NSCLC patients. Herein, we will discuss prognostic and predictive aspects of NK cells and DC cells with an emphasis on NSCLC. Additionally, the discussion will extend to potential strategies that seek to enhance the anti-tumor functionality of NK cells and DCs. 
  • 567
  • 19 Aug 2021
Topic Review
Autophagy in Cancer
Autophagy is a well-known intracellular elimination process, which provides degradation of damaged and dysfunctional organelles and proteins under highly-stressed conditions. This term came from the Greek word which represents ‘self-eating’. 
  • 567
  • 27 Oct 2021
Topic Review
Splice Site Selection Abrogated in Cancer
Splicing and alternative splicing (AS) must be tightly regulated, as they have profound effects on gene expression. Various cis-regulatory elements control the fidelity and efficiency of splicing. These include the 5′ and 3′ splice sites (SSs), splicing enhancers, splicing silencers, branch points, and polypyrimidine tracts. A quality control mechanism of splice site selection termed Suppression of Splicing (SOS), was proposed to protect cells from splicing at the numerous intronic unused, latent 5′ splice sites (LSSs) sequences, which are not used under normal growth condition. However, under stress and in cancer thousands of LSSs are activated in splicing resulting in the expression of thousands of aberrant nonsense mRNAs that may be toxic to cells. 
  • 567
  • 20 Jun 2022
Topic Review
Glioblastoma Stem Cells and Tumor Microenvironment
Glioblastoma stem cells (GSCs) are cells with a self-renewal ability and capacity to initiate tumors upon serial transplantation that have been linked to tumor cell heterogeneity. Most standard treatments fail to completely eradicate GSCs, causing the recurrence of the disease. GSCs could represent one reason for the low efficacy of cancer therapy and for the short relapse time. Nonetheless, experimental data suggest that the presence of therapy‐resistant GSCs could explain tumor recurrence. Therefore, to effectively target GSCs, a comprehensive understanding of their biology and the survival and developing mechanisms during treatment is mandatory. 
  • 567
  • 05 May 2022
Topic Review
Hypoxic Cells for Tumor Radiotherapy
Radiation therapy plays an increasingly important role in cancer treatment. It can inhibit the progression of various cancers through radiation-induced DNA breakage and reactive oxygen species (ROS) overload. Unfortunately, solid tumors, such as breast and lung cancer, often develop a hypoxic microenvironment due to insufficient blood supply and rapid tumor proliferation, thereby affecting the effectiveness of radiation therapy. Restraining hypoxia and improving the curative effect of radiotherapy have become difficult problems. Ferroptosis is a new type of cell death caused by lipid peroxidation due to iron metabolism disorders and ROS accumulation.
  • 567
  • 16 May 2022
Topic Review
Histone Deacetylases as Tumor Suppressors
Histone deacetylases (HDACs) deacetylate their targets, which leads to either the upregulation or downregulation of proteins involved in the regulation of cell cycle and apoptosis, ultimately influencing tumor growth, invasion, and drug resistance. 
  • 566
  • 26 Apr 2022
Topic Review
Biomarkers of Small Cell Lung Cancer
Small cell lung cancer (SCLC) is a high-grade neuroendocrine malignancy with an aggressive behavior and dismal prognosis. 5-year overall survival remains a disappointing 7%. Genomically, SCLCs are homogeneous compared to non-small cell lung cancers and are characterized almost always by functional inactivation of RB1 and TP53 with no actionable mutations. Additionally, SCLCs histologically appear uniform. Thus, SCLCs are managed as a single disease with platinum-based chemotherapy remaining the cornerstone of treatment. Recent studies have identified expression of dominant transcriptional signatures which may permit classification of SCLCs into four biologically distinct subtypes, namely, SCLC-A, SCLC-N, SCLC-P, and SCLC-I. These groups are readily detectable by immunohistochemistry and also have potential predictive utility for emerging therapies, including PARPi, immune checkpoint inhibitors, and DLL3 targeted therapies. In contrast with their histology, studies have identified that SCLCs display both inter- and intra-tumoral heterogeneity. Identification of subpopulations of cells with high expression of PLCG2 has been linked with risk of metastasis. SCLCs also display subtype switching under therapy pressure which may contribute furthermore to metastatic ability and chemoresistance. 
  • 566
  • 26 Oct 2022
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