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Topic Review
Mismatch Repair Deficiency
Universal MMR/MSI testing is standard of care for all patients with newly diagnosed CRC based on multi-society guidelines in the United States. Such testing is intended to identify patients with Lynch Syndrome due to a germline mutation in an MMR gene, but also detects those with sporadic dMMR/MSI-high CRCs.
  • 1.1K
  • 19 Feb 2021
Topic Review
ADAR-Mediated Site-Specific RNA Editing in Immune-Related Disease
ADAR (Adenosine Deaminases Acting on RNA) proteins are a group of enzymes that play a vital role in RNA editing by converting adenosine to inosine in RNAs. This process is a frequent post-transcriptional event observed in metazoan transcripts. Recent studies indicate widespread dysregulation of ADAR-mediated RNA editing across many immune-related diseases, such as human cancer. 
  • 1.1K
  • 09 Jan 2024
Topic Review
Tumor Suppressor WT1
The Wilms’ tumor 1 (WT1) gene was originally identified based on its mutational inactivation in Wilms’ tumor (nephroblastoma). This first discovery of WT1 as the responsible gene in an autosomal-recessive condition classified it as a tumor-suppressor gene. Mutations of WT1 were associated with the development of kidney tumors and urogenital defects.
  • 1.1K
  • 26 Jul 2021
Topic Review
Microbiota Modulation in Cancer Survivors
Chemotherapy, targeting not only malignant but also healthy cells, causes many undesirable side effects in cancer patients. Interventions and supportive care for treatment-induced late effects remain an emerging area of research in long-term cancer survivors. Due to the lack of preventive measures and approved pharmacological agents, different possibilities in preventing or mitigating the late toxicities need to be assessed. Targeting the gut microbiome in cancer survivors might represent a new potential trend being in its infancy to date. Gut microbiota disruption after chemo- and radiotherapy can be recovered by several mechanisms including administration of probiotics and/or prebiotics and FMT. Interestingly, the relationship between diet, physical activity, and gut microbiome appears to be another potential tool in cancer survivors. However, most of the data dealing with neuro- and cardioprotective effects of microbiota modulation came from preclinical and non-cancer patients´ clinical studies, and further evaluations in cancer patients are highly warranted.
  • 1.1K
  • 08 Mar 2021
Topic Review
Proteolysis-Targeting Chimeras
The ubiquitin–proteasome system (UPS) is an essential part of the cellular machinery responsible for maintaining intracellular protein homeostasis. A network of proteins that comprises the proteolytic system and chaperones calculates cellular protein homeostasis. Chaperones are in charge of correcting protein misfolding, but the proteolytic system, which converges on the 26S proteasome, is in charge of removing damaged or unfolded proteins to maintain a healthy environment inside the cell. Using proteolysis-targeting chimera (PROTAC) technology for targeted protein degradation, a novel technique of treatment is emerging that stems from an aberrant expression of a protein that causes disease. PROTAC molecules are tiny, bifunctional molecules that bind an E3-ubiquitin ligase and a target protein at the same time, causing ubiquitination and proteasome destruction of the target protein.
  • 1.1K
  • 22 May 2023
Topic Review
Therapies for Periocular Malignant Tumours
The management of periocular skin malignant tumours is challenging. Surgery remains the mainstay of treatment for localised eyelid cancers. For more locally advanced cancers, especially those invading the orbit, orbital exenteration has long been considered the gold standard; however, it is a highly disfiguring and traumatic surgery. The last two decades have been marked by the emergence of a new paradigm shift towards the use of ‘eye-sparing’ strategies. In the early 2000s, the first step consisted of performing wide conservative eyelid and orbital excisions. Multiple flaps and grafts were needed, as well as adjuvant radiotherapy in selected cases. Although being incredibly attractive, several limitations such as the inability to treat the more posteriorly located orbital lesions, as well as unbearable diplopia, eye pain and even secondary eye loss were identified. Therefore, surgeons should distinguish ‘eye-sparing’ from ‘sight-sparing’ strategies. The second step emerged over the last decade and was based on the development of targeted therapies and immunotherapies. Their advantages include their potential ability to treat almost all tumours, regardless of their locations, without performing complex surgeries. However, several limitations have been reported, including their side effects, the appearance of primary or secondary resistances, their price and the lack of consensus on treatment regimen and exact duration. 
  • 1.1K
  • 23 Jun 2021
Topic Review
Pyroptotic Cell Death Pathways
Cancer is a category of diseases involving abnormal cell growth with the potential to invade other parts of the body. Chemotherapy is the most widely used first-line treatment for multiple forms of cancer. Chemotherapeutic agents act via targeting the cellular apoptotic pathway. However, cancer cells usually acquire chemoresistance, leading to poor outcomes in cancer patients. For that reason, it is imperative to discover other cell death pathways for improved cancer intervention. Pyroptosis is a new form of programmed cell death that commonly occurs upon pathogen invasion. Pyroptosis is marked by cell swelling and plasma membrane rupture, which results in the release of cytosolic contents into the extracellular space. Currently, pyroptosis is proposed to be an alternative mode of cell death in cancer treatment. Accumulating evidence shows that the key components of pyroptotic cell death pathways, including inflammasomes, gasdermins and pro-inflammatory cytokines, are involved in the initiation and progression of cancer. Interfering with pyroptotic cell death pathways may represent a promising therapeutic option for cancer management. 
  • 1.1K
  • 28 Sep 2021
Topic Review
Immunomodulation in Pancreatic Cancer
The majority of pancreatic cancer patients have a poor prognosis, where the five-year survival rate is 9% in the United States, with an increasing incidence rate of 1.03% per year. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of pancreatic cancer that makes up 90% of all diagnosed cases of pancreatic cancer. Other types of pancreatic cancer, such as neuroendocrine tumors, which secrete insulin, or acinar carcinomas, which release digestive enzymes, are less common. PDAC develops from neoplasms of the cells lining the pancreatic ducts and usually presents without symptoms until advanced stages of the disease. Here we discuss strategies for immunomodulation of pancreatic cancer.
  • 1.1K
  • 26 Nov 2020
Topic Review
Tumor-Associated Trypsin Inhibitor (TATI)
TATI, also known as pancreatic secretory trypsin inhibitor (PSTI) or serine peptidase inhibitor Kazal 1 type (SPINK1), is a trypsin inhibitor that functions mainly in the pancreas, where it serves as a suppressor of premature trypsinogen activation.
  • 1.1K
  • 22 Sep 2021
Topic Review
Immune Microenvironment of Malignant Gliomas
Single-cell technologies allow precise identification of tumor composition at the single-cell level, providing high-resolution insights into the intratumoral heterogeneity and transcriptional activity of cells in the tumor microenvironment (TME) that previous approaches failed to capture. Malignant gliomas, the most common primary brain tumors in adults, are genetically heterogeneous and their TME consists of various stromal and immune cells playing an important role in tumor progression and responses to therapies. Previous gene expression or immunocytochemical studies of immune cells infiltrating TME of malignant gliomas failed to dissect their functional phenotypes. Single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) are powerful techniques allowing quantification of whole transcriptomes or >30 protein targets in individual cells. Both methods provide unprecedented resolution of TME. 
  • 1.1K
  • 17 Sep 2021
Topic Review
Antibody-Based Immunotherapy for Metastatic Melanoma
Melanoma is the least common form of skin cancer and is associated with the highest mortality. Where melanoma is mostly unresponsive to conventional therapies (e.g., chemotherapy), BRAF inhibitor treatment has shown improved therapeutic outcomes. Photodynamic therapy (PDT) relies on a light-activated compound to produce death-inducing amounts of reactive oxygen species (ROS). Their capacity to selectively accumulate in tumor cells has been confirmed in melanoma treatment with some encouraging results. However, this treatment approach has not reached clinical fruition for melanoma due to major limitations associated with the development of resistance and subsequent side effects. These adverse effects might be bypassed by immunotherapy in the form of antibody–drug conjugates (ADCs) relying on the ability of monoclonal antibodies (mAbs) to target specific tumor-associated antigens (TAAs) and to be used as carriers to specifically deliver cytotoxic warheads into corresponding tumor cells. Of late, the continued refinement of ADC therapeutic efficacy has given rise to photoimmunotherapy (PIT) (a light-sensitive compound conjugated to mAbs), which by virtue of requiring light activation only exerts its toxic effect on light-irradiated cells.
  • 1.1K
  • 26 Oct 2020
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. 
  • 1.1K
  • 02 Apr 2022
Topic Review
CAR T Cell Locomotion in Solid Tumor Microenvironment
The promising outcomes of chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies potentiates its capability in the fight against many cancers. Nevertheless, this immunotherapy modality needs significant improvements for the treatment of solid tumors. Researchers have incrementally identified limitations and constantly pursued better CAR designs. However, even if CAR T cells are armed with optimal killer functions, they must overcome and survive suppressive barriers imposed by the tumor microenvironment (TME). The ability of CAR T cells to efficiently migrate to the tumor site, infiltrate suppressive barriers, and survive the harsh TME represents a crucial prerequisite for carrying out the anti-tumor function.
  • 1.1K
  • 05 Jul 2022
Topic Review
Metformin Protects Livers against NASH-related-HCC
Nonalcoholic fatty liver disease (NAFLD) is strongly linked to the global epidemic of obesity and type 2 diabetes mellitus (T2DM). Notably, NAFLD can progress from the mildest form of simple steatosis to nonalcoholic steatohepatitis (NASH) that increases the risk for hepatocellular carcinoma (HCC), which is a malignancy with a dismal prognosis and rising incidence in the United States and other developed counties, possibly due to the epidemic of NAFLD. Metformin, the first-line drug for T2DM, has been suggested to reduce risks for several types of cancers including HCC and protect against NASH-related HCC, as revealed by epidemical studies on humans and preclinical studies on animal models.
  • 1.1K
  • 12 Oct 2021
Topic Review
Innate Immunity in Breast Cancer
The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer (BC). These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified.
  • 1.1K
  • 27 Oct 2020
Topic Review
Cytoskeleton Reorganization in EndMT
EndMT-derived cells, known as the myofibroblasts or cancer-associated fibroblasts (CAFs), are characterized by the loss of cell–cell junctions, loss of endothelial markers, and gain in mesenchymal ones.
  • 1.1K
  • 16 Nov 2021
Topic Review
Small-Cell Lung Cancer
Small-cell lung cancer (SCLC) is an aggressive type of cancer with an incidence of about 15% among lung cancers and has a very poor prognosis due to its rapid development of resistance to chemo- and radiotherapies. Unlike the increase in personalized approaches to the clinical care of patients with non-small-cell lung cancer (NSCLC), clinical protocols for SCLC still mainly depend on the stage of the disease, prior therapies, and lack of specific molecular support. This approach was mainly due to the idea of SCLC as a monolithic entity with common genetic features, which was strictly linked to the lack of an adequate quantity of tissue samples in this inoperable class of patients, for the lack of a clear and comprehensive biological profile presented an obstacle.
  • 1.1K
  • 22 Sep 2021
Topic Review
Nitroaromatic Hypoxia-Activated Prodrugs for Cancer Therapy
The presence of “hypoxic” tissue (with O2 levels of <0.1 mmHg) in solid tumours, resulting in quiescent tumour cells distant from blood vessels, but capable of being reactivated by reoxygenation following conventional therapy (radiation or drugs), have long been known as a limitation to successful cancer chemotherapy. This has resulted in a sustained effort to develop nitroaromatic “hypoxia-activated prodrugs” designed to undergo enzyme-based nitro group reduction selectively in these hypoxic regions, to generate active drugs. Such nitro-based prodrugs can be classified into two major groups; those activated either by electron redistribution or by fragmentation following nitro group reduction, relying on the extraordinary difference in electron demand between an aromatic nitro group and its reduction products. 
  • 1.1K
  • 22 Apr 2022
Topic Review
Antigen Targeted Therapy for LS
Lynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are hereditary disorders which significantly increase a person’s risk of developing a variety of cancers such as colorectal, endometrial, brain and, for CMMRD also, haematological malignancies. This increased cancer risk is due to inherited mutations in specific types of DNA repair genes, which hampers repair of mispaired or damaged bases during DNA replication. As a consequence, somatic mutations rapidly accumulate and typically include insertions and deletions (indels) in microsatellites that potentially can give rise to neoantigens. These neoantigens open up avenues for neoantigen-targeting immune therapies.
  • 1.1K
  • 23 Jun 2021
Topic Review
Lewy Body Dementias
Lewy body dementias (LBDs) consist of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), which are clinically similar syndromes that share neuropathological findings with widespread cortical Lewy body deposition, often with a variable degree of concomitant Alzheimer pathology. The objective of this article is to provide an overview of the neuropathological and clinical features, current diagnostic criteria, biomarkers, and management of LBD. Literature research was performed using the PubMed database, and the most pertinent articles were read and are discussed in this paper. The diagnostic criteria for DLB have recently been updated, with the addition of indicative and supportive biomarker information. The time interval of dementia onset relative to parkinsonism remains the major distinction between DLB and PDD, underpinning controversy about whether they are the same illness in a different spectrum of the disease or two separate neurodegenerative disorders. The treatment for LBD is only symptomatic, but the expected progression and prognosis differ between the two entities. Diagnosis in prodromal stages should be of the utmost importance, because implementing early treatment might change the course of the illness if disease-modifying therapies are developed in the future. Thus, the identification of novel biomarkers constitutes an area of active research, with a special focus on α-synuclein markers. 
  • 1.1K
  • 16 Sep 2023
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