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Topic Review
Gal-9/TIM-3 Immune Checkpoint with α-Lactose
The disaccharide lactose is an excipient commonly used in pharmaceutical products. The two anomers, α- and β-lactose (α-L/β-L), differ by the orientation of the C-1 hydroxyl group on the glucose unit. In aqueous solution, a mutarotation process leads to an equilibrium of about 40% α-L and 60% β-L at room temperature.
  • 1.0K
  • 04 Jan 2022
Topic Review
AXL Receptor in Breast Cancer
Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family.
  • 1.0K
  • 24 Nov 2020
Topic Review
PRMT5 in MYC-Amplified Medulloblastoma
MYC amplification or overexpression is most common in Group 3 medulloblastomas and is positively associated with poor clinical outcomes. Protein arginine methyltransferase 5 (PRMT5) overexpression has been shown to be associated with tumorigenic MYC functions in cancers, particularly in brain cancers such as glioblastoma and medulloblastoma. PRMT5 regulates oncogenes, including MYC, that are often deregulated in medulloblastomas. However, the role of PRMT5-mediated post-translational modification in the stabilization of these oncoproteins remains poorly understood. The potential impact of PRMT5 inhibition on MYC makes it an attractive target in various cancers. PRMT5 inhibitors are a promising class of anti-cancer drugs demonstrating preclinical and preliminary clinical efficacies. 
  • 1.0K
  • 03 Jan 2024
Topic Review
Immuno-PET
“Immuno-PET” merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. 
  • 1.0K
  • 06 May 2021
Topic Review
Adjuvant Therapy for Renal Cell Carcinoma
Renal cell carcinoma (RCC) is the third most common genitourinary cancer accounting for approximately 180,000 deaths worldwide in 2020. Although over two-thirds of patients initially present localized disease, up to 50% of them may progress to metastatic disease. Adjuvant therapy aims to reduce the recurrence risk and improve outcomes in several types of cancers but is currently an unmet need in RCC. RCC led to the evaluation of these target therapies in an early setting with conflicting results for disease-free survival and no overall survival (OS) benefit. 
  • 1.0K
  • 02 Mar 2023
Topic Review
Tumor Microenvironment in Basal and Squamous Cell Carcinoma
It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively.
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  • 11 May 2023
Topic Review
Near Infrared Photoimmunotherapy
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that uses an antibody-photoabsorber (IRDye700DX) conjugate (APC) that is activated by NIR light irradiation. A major benefit of NIR-PIT is that only APC-bound cancer cells that are exposed to NIR light are killed by NIR-PIT; thus, minimal damage occurs in adjacent normal cells. NIR-PIT has now been applied to many cancers expressing various cell-surface target proteins using monoclonal antibodies designed to bind to them. Moreover, NIR-PIT is not limited to tumor antigens but can also be used to kill specific host cells that create immune-permissive environments in which tumors grow. Moreover, multiple targets can be treated simultaneously with NIR-PIT using a cocktail of APCs. NIR-PIT has great potential to treat a wide variety of cancers by targeting appropriate tumor cells, immune cells, or both, and can be augmented by other immunotherapies. 
  • 1.0K
  • 23 Jun 2021
Topic Review
Functional Decline in the Older Cancer Patient
A decline in functional status, an individual’s ability to perform the normal activities required to maintain adequate health and meet basic needs, is part of normal ageing. Functional decline, however, appears to be accelerated in older patients with cancer. Such decline can occur as a result of a cancer itself, cancer treatment-related factors, or a combination of the two. The accelerated decline in function seen in older patients with cancer can be slowed, or even partly mitigated through routine assessments of functional status and timely interventions where appropriate. This is particularly important given the link between functional decline and impaired quality of life, increased mortality, comorbidity burden, and carer dependency.
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  • 11 Apr 2022
Topic Review
IPSC-Based PDAC Models and Immunotherapies
Advances in the treatment of pancreatic ductal adenocarcinoma (PDAC) using neoadjuvant chemoradiotherapy, chemotherapy, and immunotherapy have had minimal impact on the overall survival of patients. A general lack of immunogenic features and a complex tumor microenvironment (TME) are likely culprits for therapy refractoriness in PDAC. Induced pluripotent stem cells (iPSCs) should be explored as a means to advance the treatment options for PDAC, by providing representative in vitro models of pancreatic cancer development. In addition, iPSCs could be used for tailor-made cellular immunotherapies or as a source of tumor-associated antigens in the context of vaccination.
  • 1.0K
  • 29 Mar 2022
Topic Review
Biomarkers for Hepatocellular Carcinoma Diagnosis/Prognosis
Hepatocellular carcinoma (HCC) causes many deaths worldwide, and current treatments have limitations. Immunotherapies have shown the most promising clinical outcomes for advanced HCC. However, there are many patients with HCC who still respond poorly to these treatments. Circulating biomarkers that can easily be obtained through blood sampling are promising in predicting treatment responses, since they are minimally invasive and enable us to constantly monitor disease progression. 
  • 1.0K
  • 28 Sep 2021
Topic Review
Immunosuppression in Colorectal Cancer
More emerging studies are exploring immunotherapy for solid cancers, including colorectal cancer. Besides, checkpoint blockade immunotherapy and chimeric antigen receptor (CAR) -based immune cell therapy have being examined in clinical trials for colorectal cancer patients. However, immunosuppression that leads to the blockage of normal immunosurveillance often leads to cancer development and relapse.
  • 1.0K
  • 12 Jan 2021
Topic Review
Targeting SUMO Pathway in Cancer
SUMOylation is a dynamic and reversible post-translational modification, characterized more than 20 years ago, that regulates protein function at multiple levels. Due to the reversible nature of this post-translational protein modification, the balance between SUMOylation and the removal of SUMO is critical. SUMO pathway regulates the hallmark properties of cancer cells. Moreover, alterations in activity and in levels of SUMO machinery components have been observed in human cancer. Many molecular mechanisms relevant to the pathogenesis of specific cancers involve SUMO, highlighting the potential relevance of SUMO machinery components as therapeutic targets. Early-phase clinical trials are currently evaluating the safety and efficacy of SUMO pathway inhibition in cancer patients.
  • 1.0K
  • 22 Sep 2021
Topic Review
Biliary Tract Cancer Management
Biliary tract cancers (BTC) comprise a group of malignancies originating in the epithelium of the biliary tract. These include cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC). Intrahepatic cholangiocarcinoma or iCCA refers to tumors proximal to the second-order ducts, while extrahepatic cholangiocarcinoma or eCCA refers to tumors arising more distally (perihilar CCA, between second-order ducts and cystic duct and distal CCA, distal to cystic duct). Perihilar CCA represents 50% of the total CCAs, with distal lesions comprising 40% and the final 10% being intrahepatic. BTC are often diagnosed at advanced stages and have a grave outcome due to limited systemic options. Gemcitabine and cisplatin combination (GC) has been the first-line standard for more than a decade. Second-line chemotherapy (CT) options are limited. Targeted therapy or TT (fibroblast growth factor 2 inhibitors or FGFR2, isocitrate dehydrogenase 1 or IDH-1, and neurotrophic tyrosine receptor kinase or NTRK gene fusions inhibitors) have had reasonable success, but <5% of total BTC patients are eligible for them. The use of immune checkpoint inhibitors (ICI) such as pembrolizumab is restricted to microsatellite instability high (MSI-H) patients in the first line. The success of the TOPAZ-1 trial (GC plus durvalumab) is promising, with numerous trials underway that might soon bring targeted therapy (pemigatinib and infrigatinib) and ICI combinations (with CT or TT in microsatellite stable cancers) in the first line.
  • 1.0K
  • 20 May 2022
Topic Review
Application of mRNA Technology in Cancer Therapeutics
mRNA-based therapeutics pose as promising treatment strategies for cancer immunotherapy. Improvements in materials and technology of delivery systems have helped to overcome major obstacles in generating a sufficient immune response required to fight a specific type of cancer. Several in vivo models and early clinical studies have suggested that various mRNA treatment platforms can induce cancer-specific cytolytic activity, leading to numerous clinical trials to determine the optimal method of combinations and sequencing with already established agents in cancer treatment.
  • 1.0K
  • 02 Sep 2022
Topic Review
Sialic Acids in Cancer
The aberrant sialylation of membrane glycocalyx plays a pivotal role in the regulation of malignant cell behavior and correlates with a worse prognosis and shorter overall survival for patients. The biological and physical properties of sialome determine the negative charge and high hydrophilicity of cell membranes and thereby regulate cell–cell and cell–extracellular matrix interactions. There is increasing evidence that sialic acids influence cellular susceptibility in therapeutic management.
  • 1.0K
  • 03 Nov 2023
Topic Review
Transport Metabolons in Tumor Cells
Solid tumors are metabolically highly active tissues, which produce large amounts of acid. The acid/base balance in tumor cells is regulated by the concerted interplay between a variety of membrane transporters and carbonic anhydrases (CAs), which cooperate to produce an alkaline intracellular, and an acidic extracellular, environment, in which cancer cells can outcompete their adjacent host cells. Many acid/base transporters form a structural and functional complex with CAs, coined “transport metabolon”. Transport metabolons with bicarbonate transporters require the binding of CA to the transporter and CA enzymatic activity. In cancer cells, these bicarbonate transport metabolons have been attributed a role in pH regulation and cell migration. Another type of transport metabolon is formed between CAs and monocarboxylate transporters, which mediate proton-coupled lactate transport across the cell membrane. In this complex, CAs function as “proton antenna” for the transporter, which mediate the rapid exchange of protons between the transporter and the surroundings. These transport metabolons do not require CA catalytic activity, and support the rapid efflux of lactate and protons from hypoxic cancer cells to allow sustained glycolytic activity and cell proliferation.
  • 1.0K
  • 07 Jun 2021
Topic Review
Common Cardiotoxicity Manifestations
Common cardiotoxicity complications include new or worsening left ventricular ejection fraction (LVEF), QT interval prolongation, myocardial ischaemia, hypertension, thromboembolic disease, cardiac device malfunction and valve disease. Baseline electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are routinely performed for all patients commenced on cardiotoxic treatment, while other imaging modalities and biochemical markers have proven useful for monitoring. Management mainly includes early risk stratification and prompt identification of cardiovascular complications, with patient-specific surveillance throughout treatment.
  • 1.0K
  • 16 Oct 2023
Topic Review
Orexins/Hypocretins and Cancer
Orexin neuropeptides (Orexin-A/hypocretin-1 and Orexin-B/hypocretins-2) produced from the same precursor in hypothalamus. These two neurotransmitters and their receptors (OX1R and OX1R), present in the central and peripheral nervous system, play a major role in wakefulness but also in drug addiction, food consumption, homeostasis, hormone secretion, reproductive function, lipolysis and blood pressure regulation. With respect to these biological functions, orexins were involved in various pathologies encompassing narcolepsy, neurodegenerative diseases, chronic inflammations, metabolic syndrome and cancers. The expression of OX1R in various cancers including colon, pancreas and prostate cancers associated with its ability to induce a proapoptotic activity in tumor cells, suggested that the orexins/OX1R system could have a promising therapeutic role.
  • 1.0K
  • 03 Sep 2021
Topic Review
β-Catenin and Hepatocellular Cancer
Hepatocellular cancer (HCC), the most common primary liver tumor, has been gradually growing in incidence globally. The whole-genome and whole-exome sequencing of HCC has led to an improved understanding of the molecular drivers of this tumor type. Activation of the Wnt signaling pathway, mostly due to stabilizing missense mutations in its downstream effector β-catenin (encoded by CTNNB1) or loss-of-function mutations in AXIN1 (the gene which encodes for Axin-1, an essential protein for β-catenin degradation), are seen in a major subset of HCC. 
  • 1.0K
  • 28 Apr 2021
Topic Review
Small Extracellular Vesicles
Small Extracellular Vesicles are lipid bilayer structures ranging in size from 15 to 10,000 nm, are released from almost all cells (normal and cancerous) present in body fluids, and they are considered as delivery vehicles responsible for local and distant cellular communication.
  • 1.0K
  • 17 Dec 2020
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