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Topic Review
Perineural Invasion and the Perineural Niche
Perineural invasion (PNI) is a very well known process by pathologists and one the most actively studied events in cancer–nerve relations at the molecular level. The discrete microenvironment surrounding an invaded nerve, also called the perineural niche, is formed by neural cells, supporting cells, inflammatory cells, extracellular matrix, blood vessels, and immune components.
  • 952
  • 06 Dec 2022
Topic Review
Mechanism of Action of Lymphocyte Activation Gene 3
Lymphocyte activation gene 3 (LAG-3) (CD223) is a CD4-related activation-induced cell surface inhibitory receptor that binds to major histocompatibility complex (MHC) class II molecules with high affinity and negatively regulates T cell effector functions. 
  • 952
  • 21 Aug 2023
Topic Review
ALT Positivity in Human Cancers
Neoplastic cells typically activate one of the two Telomere Maintenance Mechanisms(TMM) to maintain their telomeres during uncontrolled proliferation. Most tumors reactivatetelomerase, a high-fidelity DNA transferase with reverse transcriptase activity. The prevalence of telomerase positive cancers is at 80–90% of all malignancies. A significant percentage of neoplasias activate the second type of TMM, called alternativelengthening of telomeres (ALT), to achieve replicative immortality and telomereelongation. ALT is commonly thought to occur in about 10–20% of all tumors. Unlike the TEL+ tumors, which rely on the enzymatic activity of a single enzyme,ALT relies on many DNA damage response (DDR) proteins, including those involved inthe homology-dependent repair (HDR) pathway.
  • 952
  • 23 Jun 2021
Topic Review
Colorectal Cancer Stem Cells
Colorectal cancer stem cells (CCSCs) is a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology.
  • 952
  • 18 Feb 2021
Topic Review
Glucose Transporters and Breast Cancer
Reprogramming of cellular energy metabolism is widely accepted to be a cancer hallmark. The deviant energetic metabolism of cancer cells-known as the Warburg effect-consists in much higher rates of glucose uptake and glycolytic oxidation coupled with the production of lactic acid, even in the presence of oxygen. Consequently, cancer cells have higher glucose needs and thus display a higher sensitivity to glucose deprivation-induced death than normal cells. So, inhibitors of glucose uptake are potential therapeutic targets in cancer. Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer death in women worldwide. Overexpression of facilitative glucose transporters (GLUT), mainly GLUT1, in breast cancer cells is firmly established, and the consequences of GLUT inhibition and/or knockout are under investigation.
  • 951
  • 09 Jul 2021
Topic Review
Delta Radiomics in Head and Neck Cancers
Delta (Δ) radiomics, a concept based on the variation of parameters extracted from medical imaging using artificial intelligence (AI) algorithms, demonstrates its potential as a predictive biomarker of treatment response in head and neck cancers (HNC). The concept of image-guided radiotherapy (IGRT), including computer tomography simulation (CT) and position control imaging with cone-beam-computed tomography (CBCT), now offers new perspectives for radiomics applied in radiotherapy. The use of Δ features of texture, shape, and size, both from the primary tumor and from the tumor-involved lymph nodes, demonstrates the best predictive accuracy. If, in the case of treatment response, promising Δ radiomics results could be obtained, even after 24 h from the start of treatment, for radiation-induced xerostomia, the evaluation of Δ radiomics in the middle of treatment could be recommended. 
  • 951
  • 30 Jun 2023
Topic Review
Atherosclerosis, Diabetes Mellitus, and Cancer
The involvement of cardiovascular disease in cancer onset and development represents a contemporary interest in basic science. It has been recognized, from the most recent research, that metabolic syndrome-related conditions, ranging from atherosclerosis to diabetes, elicit many pathways regulating lipid metabolism and lipid signaling that are also linked to the same framework of multiple potential mechanisms for inducing cancer.
  • 951
  • 26 Jul 2023
Topic Review
Simultaneous Monitoring of Multi-Enzyme Activity
The use of fluorescent imaging probes that monitor the activity of proteases that experience an increase in expression and activity in tumors is well established. These probes can be conjugated to nanoparticles of iron oxide, creating a multimodal probe serving as both a magnetic resonance imaging (MRI) agent and an indicator of local protease activity. Previous works describe probes for cathepsin D (CatD) and metalloproteinase-2 (MMP2) protease activity grafted to cross-linked iron oxide nanoparticles (CLIO). Herein, we have synthesized a triply labeled fluorescent iron oxide nanoparticle molecular imaging (MI) probe, including an AF750 substrate concentration reporter along with probes for cathepsin B (CatB) sand MMP2 protease activity. The reporter provides a baseline signal from which to compare the activity of the two proteases. The activity of the MI probe was verified through incubation with the proteases and tested in vitro using the human HT29 tumor cell line and in vivo using female nude mice injected with HT29 cells. We found the MI probe had the appropriate specificity to the activity of their respective proteases, and the reporter dye did not activate when incubated in the presence of only MMP2 and CatB. Probe fluorescent activity was confirmed in vitro, and reporter signal activation was also noted. The fluorescent activity was also visible in vivo, with injected HT29 cells exhibiting fluorescence, distinguishing them from the rest of the animal. The reporter signal was also observable in vivo, which allowed the signal intensities of the protease probes to be corrected; this is a unique feature of this MI probe design.
  • 950
  • 30 Oct 2020
Topic Review
Metastatic Castration-Resistant Prostate Cancer
Although most prostate cancers are localized, and the majority are curable, recurrences occur in approximately 35% of men. Among patients with prostate-specific antigen (PSA) recurrence and PSA doubling time (PSADT) less than 15 months after radical prostatectomy, prostate cancer accounted for approximately 90% of the deaths by 15 years after recurrence. An immunosuppressive tumor microenvironment (TME) and impaired cellular immunity are likely largely responsible for the limited utility of checkpoint inhibitors (CPIs) in advanced prostate cancer compared with other tumor types. Thus, for immunologically “cold” malignancies such as prostate cancer, clinical trial development has pivoted towards novel approaches to enhance immune responses. Numerous clinical trials are currently evaluating combination immunomodulatory strategies incorporating vaccine-based therapies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T cells. Other trials evaluate the efficacy and safety of these immunomodulatory agents’ combinations with standard approaches such as androgen deprivation therapy (ADT), taxane-based chemotherapy, radiotherapy, and targeted therapies such as tyrosine kinase inhibitors (TKI) and poly ADP ribose polymerase (PARP) inhibitors.
  • 950
  • 01 Feb 2021
Topic Review
FOXO3 as a Novel Biomarker in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) represents one of the main causes of cancer-related death worldwide. The transcription factor forkhead box O3 (FOXO3) has been related to hepatic diseases and tumor progression, but the exact role played by FOXO3 on HCC still remains unclear. Recently, a novel systematic review with meta-analysis revealed the potential diagnostic and prognostic value of FOXO3 in this primary liver cancer type.
  • 950
  • 05 Nov 2021
Topic Review
Genetic Therapy in Oncology
The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes—mainly targeted therapy, immunomodulatory therapy, and gene therapy. 
  • 950
  • 03 Nov 2023
Topic Review
Survival in Metastatic Prostate Cancer
The real-world survival trends are largely unexplored in patients with de novo metastatic prostate cancer. A recent population-based analysis provided data about the survival improvements in patients with de novo metastatic prostate cancer diagnosed in USA between 2000 and 2014. Despite the advent of several new drugs, limited improvements in overall and cancer-specific survival were observed in 2011-2014 compared to 2000-2003 and 2004-2010.
  • 950
  • 27 Oct 2020
Topic Review
EDCs function in tumor microenvironment
Endocrine disruptors (EDCs) can display estrogenic and androgenic effects, and their exposure has been linked to increased cancer risk. EDCs have been shown to directly affect cancer cell regulation and progression, but their influence on tumour microenvironment is still not completely elucidated. In this context, the signalling hub protein RACK1 (Receptor for Activated C Kinase 1) could represent a nexus between cancer and the immune system due to its roles in cancer progression and innate immune activation. Since RACK1 is a relevant EDCs target that responds to steroid-active compounds, it could be considered a molecular bridge between the endocrine-regulated tumour microenvironment and the innate immune system.
  • 949
  • 17 Dec 2020
Topic Review
Polyphenols in Leukaemia
Leukaemia is a malignant disease of the blood. Current treatments for leukaemia are associated with serious side-effects. Here we discuss the potential therapeutic use of polyphenols in leukaemia. We outline the molecular mechanism of action of polyphenol in leukaemia cell lines, and discuss the pharmacological properties of polyphenols, including their anti-inflammatory, antioxidant, anti-proliferative, and anti-tumour activities, and suggest that polyphenols are potent natural agents that can be useful therapeutically; and discuss why data on bioavailability, toxicity and metabolism is essential to evaluate their clinical use. 
  • 949
  • 22 Sep 2021
Topic Review
β-Catenin in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the deadliest human cancers. Activating mutations in the telomerase reverse transcriptase (TERT) promoter (TERTp) and CTNNB1 gene encoding β-catenin are widespread in HCC (~50% and ~30%, respectively). TERTp mutations are predicted to increase TERT transcription and telomerase activity. 
  • 948
  • 02 Sep 2021
Topic Review
Emerging Tumor Markers in Ovarian Cancer
Ovarian cancer (OC) is characterized by silent progression and late-stage diagnosis. It is critical to detect and accurately diagnose the disease early to improve survival rates. Tumor markers have emerged as valuable tools in the diagnosis and management of OC, offering non-invasive and cost-effective options for screening, monitoring, and prognosis.
  • 948
  • 09 Aug 2023
Topic Review
Breast Cancer in Asia
Nearly all breast cancer patients survive for more than five years when the tumor is found early and in the localized stage. Regular clinical breast examinations, mammograms, and monthly self-exams of the breasts all contribute to early detection. However, late-stage breast cancers are common in many Asian countries. Low-income countries suffer from a lack of resources for breast cancer screening. Close to half (45.4%) of the 2.3 million breast cancers (BC) diagnosed in 2020 were from Asia.
  • 947
  • 09 Sep 2022
Topic Review
Similarities and Differences of RhoGDI1 and RhoGDI2
RhoGDI1 and RhoGDI2 (guanine nucleotide dissociation inhibitor (GDI)) have been implicated in multiple human cancers through their involvement in cancer cell migration, invasion and metastasis and, thus, are regarded as attractive targets for cancer biology. RhoGDI2 has largely remained in RhoGDI1′s shadow because of its lower abundancy and more restrained distribution. 
  • 947
  • 20 Mar 2023
Topic Review
Estrogen Receptors in Non Small Cell Lung Cancer
This entry highlights that exogenous and endogenous sources of estrogens in the human body.  Estrogen associated receptors ERs, GPERs, EGFRs and orphan nuclear receptors ERRs. Role of estrogens and associated receptors in normal lung physiology and NSCLC complications. Potential of using anti-estrogen molecules, alone or in combination with ER/GPER/ EGFR/ERR inhibitors as NSCLC treatment regimen.
  • 946
  • 10 Jan 2022
Topic Review
Targeted Strategies for Degradation of Key Transmembrane Proteins in Cancer
Targeted protein degradation is an attractive technology for cancer treatment due to its ability to overcome the unpredictability of the small molecule inhibitors that cause resistance mutations. Various targeted protein degradation strategies have been developed based on the ubiquitin–proteasome system in the cytoplasm or the autophagy–lysosomal system during endocytosis. Here describe technologies for the targeted inhibition and targeted degradation of the epidermal growth factor receptor (EGFR), one of the major transmembrane proteins responsible for the onset and progression of many types of cancer.
  • 946
  • 21 Sep 2023
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