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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. 
  • 1.2K
  • 23 Jun 2021
Topic Review
Exosomes in Cancer Therapy
Exosomes are nano-vesicle-shaped particles secreted by various cells, including cancer cells.  Many studies have focused on the bioactive molecules that they export as exosomal cargo. These molecules can function as biomarkers in diagnosis or play a relevant role in modulating the immune system and in promoting apoptosis, cancer development and progression.
  • 1.2K
  • 22 Sep 2021
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.
  • 1.2K
  • 05 Jul 2022
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.
  • 1.2K
  • 22 May 2023
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
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
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
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
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
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
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
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
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. 
  • 1.1K
  • 19 Oct 2023
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
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
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
Protein Tyrosine Phosphatases
Protein tyrosine kinases, especially receptor tyrosine kinases, have dominated the cancer therapeutics sphere as proteins that can be inhibited to selectively target cancer. However, protein tyrosine phosphatases (PTPs) are also an emerging target. Though historically known as negative regulators of the oncogenic tyrosine kinases, PTPs are now known to be both tumor-suppressive and oncogenic.
  • 1.1K
  • 07 Dec 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
Circulating Tumor Cells in Colorectal Cancer
Circulating tumor cells (CTCs)  are intact cells separated from the primary tumor or metastases and released into the peripheral circulation. They were observed and discovered for the first time in 1869 in the blood of a patient with breast cancer. CTCs mainly originate from solid tumors of epithelial origin (breast, prostate, colon, and lung). CTCs are nucleated and express epithelial cell adhesion molecules (EpCAM) and/or cytokeratins (CK) in the cytoplasm without coexpressing the common leukocyte antigen CD45. It is known today that there is significant heterogeneity in cell species and surface markers, which represents a challenge in isolating all clinically relevant subpopulations of CTCs.
  • 1.1K
  • 22 Nov 2022
Topic Review
Metabolic Reprogramming in Tumor Endothelial Cells
The dynamic crosstalk between the different components of the tumor microenvironment is critical to determine cancer progression, metastatic dissemination, tumor immunity, and therapeutic responses. Angiogenesis is critical for tumor growth, and abnormal blood vessels contribute to hypoxia and acidosis in the tumor microenvironment. In this hostile environment, cancer and stromal cells have the ability to alter their metabolism in order to support the high energetic demands and favor rapid tumor proliferation. 
  • 1.1K
  • 12 Oct 2022
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