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Topic Review
Tumor-Associated Carbohydrate Antigen-Targeted Immunotherapy
Glycosylation is one of the most pivotal post-translational modifications on all types of biomolecules for the formation of glycoproteins, glycolipids, and glycoRNAs in a tissue-type specific manner. Normal glycans participate in biological events such as development, metabolism, differentiation, and immunity in mammalian cells. In cancers, the altered glycosylation, known as tumor-associated carbohydrate antigens (TACAs), is specifically expressed on cell surface molecules and play important roles in facilitating tumor formation, progression, metastasis, and immunosurveillance evasion by generating the vulnerable tumor microenvironment through the interaction of glycan binding receptors expressed on immune cells. TACAs are potential tumor glyco-biomarkers, glycoimmune checkpoints, and therapeutics.
  • 1.3K
  • 17 Jul 2023
Topic Review
ESR1 Mutations
The ESR1 gene located at 6q25.1–q25.2 encodes an ER and a ligand-activated transcription factor consisting of several domains involved in hormone binding.
  • 1.3K
  • 18 Dec 2020
Topic Review
DNA Damage Response
Genomic instability is responsible for the progression of acute leukemia, caused by the dysfunction of the DDR genes and activation of certain oncogenes
  • 1.3K
  • 26 Oct 2020
Topic Review
Immune Checkpoint Therapy Resistance with SHP2 Inhibition
SHP2 (Src Homology 2 Domain-Containing Phosphatase 2) is a protein tyrosine phosphatase widely expressed in various cell types. SHP2 plays a crucial role in different cellular processes, such as cell proliferation, differentiation, and survival. Aberrant activation of SHP2 has been implicated in multiple human cancers and is considered a promising therapeutic target for treating these malignancies. The PTPN11 gene and functions encode SHP2 as a critical signal transduction regulator that interacts with key signaling molecules in both the RAS/ERK and PD-1/PD-L1 pathways; SHP2 is also implicated in T-cell signaling. SHP2 may be inhibited by molecules that cause allosteric (bind to sites other than the active site and attenuate activation) or orthosteric (bind to the active site and stop activation) inhibition or via potent SHP2 degraders. These inhibitors have anti-proliferative effects in cancer cells and suppress tumor growth in preclinical models. In addition, several SHP2 inhibitors are in clinical trials for cancer treatment.
  • 1.3K
  • 22 Nov 2023
Topic Review
Rectal Cancer
Locally advanced rectal cancer represents a major health problem. Recently, the important results obtained with RAPIDO and PRODIGE 23 trials have changed the treatment algorithm of this disease.
  • 1.3K
  • 22 Dec 2020
Topic Review
Metabolic Anti-Cancer Effects of Melatonin
Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers. 
  • 1.3K
  • 08 Jul 2021
Topic Review
Targeted Therapies for Vestibular Schwannoma
Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. A clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. 
  • 1.3K
  • 26 May 2022
Topic Review
Strategies for Identification of Neoantigens
This entry provides an overview of currently available approaches applied for neoantigens discovery—tumor-specific peptides that appeared due to the mutation process and distinguish tumors from normal tissues. Focusing on genomics-based approaches and computational pipelines, we cover all steps required for selecting appropriate candidate peptides starting from NGS-derived data. Moreover, additional approaches such as mass-spectrometry-based and structure-based methods are discussed highlighting their advantages and disadvantages. This review also provides a description of available complex bioinformatics pipelines ensuring automated data processing resulting in a list of neoantigens. We propose the possible ideal pipeline that could be implemented in the neoantigens identification process. We discuss the integration of results generated by di erent approaches to improve the accuracy of neoantigens selection.
  • 1.3K
  • 08 Apr 2021
Topic Review
BRAF Mutated Colorectal Cancer
Colon cancer is one of the most frequently diagnosed malignancies in adults, considering both its incidence and prevalence. Anatomically, the right colon is considered as being from the cecum to the splenic flexure, and the left colon is from the splenic flexure to the rectum. Sidedness is a surrogate of a wide spectrum of colorectal cancer (CRC) biology features (embryology, microbiome, methylation, microsatellite instability (MSI), BRAF, aging, KRAS, consensus molecular subtypes (CMS), etc.), which result in prognostic factors. Different molecular subtypes have been identified, according to genomic and transcriptomic criteria. A subgroup harboring a BRAF mutation has been described, and represents approximately 10% of the patients diagnosed with colon cancer. This subgroup has morphological, clinical, and therapeutic characteristics that differ substantially from patients who do not carry this genetic alteration. Unfortunately, there is no established standard of care for this particular cohort of patients.
  • 1.2K
  • 14 Sep 2020
Topic Review
Asthma and Lung Cancer
A large gap still exists in our knowledge of the effects of dietary supplements on lung cancer risk/mortality in asthmatic smokers and nonsmokers. There is a lack of reliable studies for detecting such an effect says a researcher in the journal Nutrients [1]. The researcher undertook a comprehensive review of studies on the topic, and is now calling for trials and studies of these supplements to detect their benefits and harms. The best way to reduce lung cancer risk is to get those at greatest risk of lung cancer (active and passive smokers, particularly those with asthma) to stop smoking or reduce exposure to tobacco smoke. In industrial societies, airborne environmental pollutants are also risk factors. [1] Alsharairi, N. The effects of dietary supplements on Asthma and Lung Cancer risk in smokers and non-smokers: A review of the literature. Nutrients, 2019, 11, 725.
  • 1.2K
  • 03 Nov 2020
Topic Review
Major Advances and Emerging Concepts of EPR-Enhancing Strategies
The enhanced permeability and retention (EPR) effect is dynamic and a phenomenon of tumor blood vessels, which is mostly dependent on blood flow. Animal models of solid tumors rich in blood flow demonstrated enhanced EPR effects. The strategies to enhance the EPR effect can be broadly classified into pharmacological and physical-based approaches.
  • 1.2K
  • 03 Mar 2023
Topic Review
Cisplatin Resistance
Cisplatin (CDDP) is the drug of choice against different types of cancer. However, tumor cells can acquire resistance to the damage caused by cisplatin, generating genetic and epigenetic changes that lead to the generation of resistance and the activation of intrinsic resistance mechanisms in cancer cells. 
  • 1.2K
  • 18 Oct 2022
Topic Review
Significance of Mitochondrial-Dysfunction in Cancer
       Mitochondria are semi-autonomous intracellular double membrane-bound organelles, which include an outer membrane, a highly folded inner membrane (crista), a matrix space surrounded by the inner membrane, and an inter-membrane space between the inner and outer membranes. Usually, a cell has hundreds or thousands of mitochondria, which can occupy up to 25% of the cellular cytoplasm. Mitochondria are a convergence point for glucose, glutamine, and lipid metabolism. The primary function of mitochondria is to support the TCA cycle and aerobic respiration by oxidative phosphorylation, generating ATP through the mitochondrial respiratory chain to fulfill the energy needs for cell survival. One unique feature of mitochondria is that they possess their own supercoiled, double-stranded circular genetic material called mitochondrial DNA (mtDNA) that encodes rRNAs, tRNAs, and proteins essential for electron transport and oxidative phosphorylation, as well as their own genetic repair mechanisms. Mitochondrial biogenesis requires the coordinated expression of both mtDNA- and nuclear DNA-encoded genes. Thirteen proteins are encoded by mtDNA, while approximately 1000 mitochondrial proteins are encoded by the nuclear genome, translated in the cytoplasm and transported into the mitochondria by a specific transport system. These two pools of proteins are required to maintain mitochondria as a cellular power hub and a signaling nexus that are essential for normal cell function. Defects in many of the mitochondrial components are causal for a multitude of cellular diseases. Of note, the reprogramming of cellular metabolism and the aberrant redox status have been heralded as major emerging hallmarks of neoplastic transformation. Overall, mitochondrial dysfunction caused by mtDNA mutations, malfunctioned TCA cycle enzymes, electron respiratory chain leakage and subsequent oxidative stress, and/or aberrant oncogenic and tumor suppressor signaling is known to alter cellular metabolic pathways, disrupt redox balance, and cause resistance to apoptosis and therapies that significantly contribute to the development of multiple types of human cancers. In the following sections, we will present current knowledge on these aspects of mitochondrial dysfunction pertaining to the pathologies of various forms of human malignancies.
  • 1.2K
  • 27 Aug 2020
Topic Review
immunotherapeutic approaches of Prostate Cancer
The clinical spectrum of prostate cancer (PCa) varies from castration-naive to metastatic castration-resistant disease. Despite the administration of androgen synthesis inhibitors and chemotherapy regimens for castration-resistant prostate cancer, the treatment options for this entity are limited. The utilization of the immune system against cancer cells shows potential as a therapeutic modality for various solid tumors and hematologic malignancies. With technological advances over the last decade, immunotherapy has become an integral treatment modality for advanced solid tumors. The feasibility of immunotherapy has shown promise for patients with PCa, and with advances in molecular diagnostic platforms and our understanding of immune mechanisms, immunotherapy is reemerging as a potential treatment modality for PCa. Various combinations of individualized immunotherapy and immune checkpoint blockers with androgen receptor-targeted therapies and conventional cytotoxic agents show promise. This article will review the current status of immunotherapy, including new discoveries and precision approaches for PCa, and discuss future directions in the continuously evolving landscape of immunotherapy.
  • 1.2K
  • 28 Oct 2020
Topic Review
Acute Promyelocytic Leukemia in Children
Acute promyelocytic leukemia (APL) represents a paradigm of precision medicine.
  • 1.2K
  • 07 May 2021
Topic Review
The Blood–Brain Barrier and Drug Efflux Pumps
Glioblastoma (GBM) remains one of the most difficult tumors to treat. The one of major obstacle in GBM treatment is the blood–brain barrier (BBB), which prevents effective delivery of drugs to the central nervous system (CNS). Another key player impeding drug delivery into the CNS is the family of drug efflux pumps and more specifically the ATP-binding cassette (ABC) transporters. 
  • 1.2K
  • 25 Aug 2022
Topic Review
Photochemical Internalization
Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS2a). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS2a combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans.
  • 1.2K
  • 16 Jun 2021
Topic Review
Screening Prospects for Ovarian Cancer
Ovarian cancer (OC) has the highest mortality rate of all gynecologic malignancies. The overall five-year survival is 46% and varies depending on the stage and histological type of the tumor. High-grade serous carcinoma (HGSOC) accounts for 75% of all epithelial ovarian malignancies and is diagnosed mainly at FIGO stage III (51%) or IV (29%), reflecting the aggressive nature.
  • 1.2K
  • 16 Aug 2021
Topic Review
Breast Cancer Treatments
Breast cancer (BC) is the most frequent cancer diagnosed in women worldwide. This heterogeneous disease can be classified into four molecular subtypes (luminal A, luminal B, HER2 and triple-negative breast cancer (TNBC)) according to the expression of the estrogen receptor (ER) and the progesterone receptor (PR), and the overexpression of the human epidermal growth factor receptor 2 (HER2). Current BC treatments target these receptors (endocrine and anti-HER2 therapies) as a personalized treatment. Along with chemotherapy and radiotherapy, these therapies can have severe adverse effects and patients can develop resistance to these agents. Moreover, TNBC do not have standardized treatments. Hence it is essential to develop new treatments to target more effectively each BC subgroup. 
  • 1.2K
  • 06 Sep 2021
Topic Review
Epithelial–Mesenchymal Transition Involved in Transcription Factors
Transcription factors involve many proteins in the process of transactivating or transcribing (none-) encoded DNA to initiate and regulate downstream signals, such as RNA polymerase. Their unique characteristic is that they possess specific domains that bind to specific DNA element sequences called enhancer or promoter sequences. Epithelial–mesenchymal transition (EMT) is involved in cancer progression.
  • 1.2K
  • 07 Sep 2023
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