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Topic Review
Current Landscape of HER2-Targeted ADCs
Human epidermal growth factor receptor 2 (HER2) tyrosine kinase is overexpressed in 20% of breast cancers and associated with a less favorable prognosis compared to HER2-negative disease.
  • 1.1K
  • 21 Feb 2024
Topic Review
Malignant Pleural Mesothelioma
Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a rare disease with a global incidence in countries like Italy of about 1.15 per 100,000 inhabitants. Malignant Pleural Mesothelioma (MPM) is the most common form of mesothelioma, accounting for approximately 80% of disease. Although rare in the global population, mesothelioma is linked to industrial pollutants and mineral fiber exposure, with approximately 80% of cases linked to asbestos. Due to the persistent asbestos exposure in many countries, a worldwide progressive increase in MPM incidence is expected for the current and coming years. The tumor grows in a loco-regional pattern, spreading from the parietal to the visceral pleura and invading the surrounding structures that induce the clinical picture of pleural effusion, pain and dyspnea. Distant spreading and metastasis are rarely observed, and most patients die from the burden of the primary tumor. Currently, there are no effective treatments for MPM, and the prognosis is invariably poor. Some studies average the prognosis to be roughly one-year after diagnosis. The uniquely poor mutational landscape which characterizes MPM appears to derive from a selective pressure operated by the environment; thus, inflammation and immune response emerge as key players in driving MPM progression and represent promising therapeutic targets.
  • 1.1K
  • 07 Apr 2021
Topic Review
Non-Coding RNAs in Glioblastoma
Non-coding RNAs have been implicated as master regulators of several biological processes, their expression being strictly regulated under physiological conditions. In recent years, particularly in the last decade, substantial effort has been made to investigate the function of ncRNAs in several human diseases, including cancer. The aim of this review is to guide the reader through important aspects of miRNA and lncRNA biology, focusing on the molecular mechanism associated with glioblastoma onset/progression.
  • 1.1K
  • 28 Oct 2020
Topic Review
Drug Development Platform for Cholangiocarcinoma
Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains to be adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available
  • 1.1K
  • 09 Feb 2021
Topic Review
Circadian Clock and Liver Cancer
Circadian clocks control several homeostatic processes in mammals through internal molecular mechanisms. Chronic perturbation of circadian rhythms is associated with metabolic diseases and increased cancer risk, including liver cancer. The hepatic physiology follows a daily rhythm, driven by clock genes that control the expression of several proteins involved in distinct metabolic pathways. Alteration of the liver clock results in metabolic disorders, such as non-alcoholic fatty liver diseases (NAFLD) and impaired glucose metabolism, that can trigger the activation of oncogenic pathways, inducing spontaneous hepatocarcinoma (HCC). The study of oncogenic changes related to alterations of liver clock provides new potentially useful targets for prevention and management of HCC.
  • 1.1K
  • 11 Aug 2021
Topic Review
The Genetics of Pheochromocytoma and Paraganglioma
Pheochromocytoma and paraganglioma (together PPGL) are rare neuroendocrine tumors that arise from chromaffin tissue and produce catecholamines. Approximately 40% of cases of PPGL carry a germline mutation, suggesting that they have a high degree of heritability. The underlying mutation influences the PPGL clinical presentation such as cell differentiation, specific catecholamine production, tumor location, malignant potential and genetic anticipation, which helps to better understand the clinical course and tailor treatment accordingly. Genetic testing for pheochromocytoma and paraganglioma allows an early detection of hereditary syndromes and facilitates a close follow-up of high-risk patients.
  • 1.1K
  • 29 Mar 2022
Topic Review
DPP-IV Inhibition in Anticancer Treatment
Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Nevertheless, the modulation of the bioavailability and function of other DPP-IV substrates, including chemokines, raises the possibility that the use of these orally administered drugs with favorable side-effect profiles might be extended beyond the treatment of hyperglycemia. 
  • 1.1K
  • 05 May 2022
Topic Review
Strategies Directly Targeting Mutated KRAS
KRAS gene mutation is widespread in tumors and plays an important role in various malignancies. Targeting KRAS mutations is regarded as the “holy grail” of targeted cancer therapies. Multiple strategies, including covalent binding strategy, targeted protein degradation strategy, targeting protein and protein interaction strategy, salt bridge strategy, and multivalent strategy, have been adopted to develop KRAS direct inhibitors for anti-cancer therapy. Various KRAS-directed inhibitors have been developed, including the FDA-approved drugs sotorasib and adagrasib, KRAS-G12D inhibitor MRTX1133, and KRAS-G12V inhibitor JAB-23000, etc. The different strategies greatly promote the development of KRAS inhibitors. 
  • 1.1K
  • 27 Apr 2023
Topic Review
Nonsteroidal Anti-Inflammatory Drugs in Prostate Cancer
Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs (NSAIDs) along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer.
  • 1.1K
  • 13 Dec 2023
Topic Review
Pancreatic Cancer and Arterial Resection
Aggressive arterial resection (AR) in surgical treatment for locally advanced pancreatic cancer (LAPC) has gradually been encouraged thanks to new chemotherapy regimens such as FOLFIRINOX or Gemcitabine and nab-paclitaxel, which have provided more adequate patient selection and local tumor suppression justifying aggressive local resection. The development of surgical techniques provides the safety of AR for even major visceral arteries such as the celiac axis or superior mesenteric artery. 
  • 1.1K
  • 25 May 2021
Topic Review
Bone in Inherited Endocrine Tumors
Endocrine tumors are neoplasms originating from specialized hormone-secreting cells. They can develop as sporadic tumors, caused by somatic mutations, or in the context of familial Mendelian inherited diseases. Congenital forms, manifesting as syndromic or non-syndromic diseases, are caused by germinal heterozygote autosomal dominant mutations in oncogenes or tumor suppressor genes.
  • 1.1K
  • 30 Aug 2021
Topic Review
ICIs for HCC treatment
Immunotherapies are promising approaches for treating hepatocellular carcinomas (HCCs) refractory to conventional therapies. However, a recent clinical trial of immune checkpoint inhibitors (ICIs) revealed that anti-tumor responses to ICIs are not satisfactory in HCC cases. Therefore, it is critical to identify molecular markers to predict outcome and develop novel combination therapies that enhance the efficacy of ICIs. Recently, several attempts have been made to classify HCC based on genome, epigenome, and transcriptome analyses. These molecular classifications are characterized by unique clinical and histological features of HCC, as well immune phenotype. For example, HCCs exhibiting gene expression patterns with proliferation signals and stem cell markers are associated with the enrichment of immune infiltrates in tumors, suggesting immune-proficient characteristics for this type of HCC. However, the presence of activating mutations in β-catenin represents a lack of immune infiltrates and refractoriness to ICIs. Although the precise mechanism that links the immunological phenotype with molecular features remains controversial, it is conceivable that alterations of oncogenic cellular signaling in cancer may lead to the expression of immune-regulatory molecules and result in the acquisition of specific immunological microenvironments for each case of HCC. Therefore, these molecular and immune characteristics should be considered for the management of HCC using immunotherapy.
  • 1.1K
  • 02 Nov 2020
Topic Review
Contribution of Epstein–Barr Virus to Cancer Hallmarks
The concept of ‘hallmarks of cancer’ was first introduced by Hanahan and Weinberg in 2000 and represented the cellular traits through which different cancers acquire the capabilities to survive, proliferate and disseminate. Epstein–Barr virus (EBV), the first recognized human oncogenic virus in history, is one of the environmental factors that can drive oncogenesis of several lymphoid and epithelial malignancies through various hallmarks of cancer. This entry summarizes the contribution of EBV lytic proteins to cancer hallmarks and provide a framework to address the complexity of EBV-driven oncogenesis.
  • 1.1K
  • 10 Apr 2023
Topic Review
Mucinous Cancer of the Ovary
Mucinous ovarian cancer (MOC) is a rare subtype of epithelial ovarian carcinoma (EOC). Whereas all EOC subtypes are addressed in the same way, MOC is a distinct entity. Appreciating the pathological features and genomic profile of MOC may result in the improvement in management and, hence, the prognosis. Distinguishing primary MOC from metastatic mucinous carcinoma can be challenging but is essential. Early-stage MOC carries an excellent prognosis, with advanced disease having a poor outcome. Surgical management plays an essential role in the early stage and in metastatic disease. Chemotherapy is usually administered for stage II MOC and beyond. The standard gynecology protocol is frequently used, but gastrointestinal regimens have also been administered. As MOC is associated with multiple molecular alterations, targeted therapy could be the answer to treat this disease.
  • 1.1K
  • 29 Mar 2022
Topic Review
Immune Checkpoint Inhibitors in Urothelial Bladder Cancer
Bladder cancer (BC) is the most common malignancy of the genitourinary tract, with high morbidity and mortality rates. Until recently, the treatment of locally advanced or metastatic urothelial BC was based on the use of chemotherapy alone. Since 2016, five immune checkpoint inhibitors (ICIs) have been approved by the Food and Drug Administration (FDA) in different settings, i.e., first-line, maintenance and second-line treatment, while several trials are still ongoing in the perioperative context. Lately, pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been approved for Bacillus Calmette–Guérin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), using immunotherapy at an early stage of the disease.
  • 1.1K
  • 19 Jun 2023
Topic Review
SALL Proteins in Cancer
SALL proteins are a family of four conserved C2H2 zinc finger transcription factors that play critical roles in organogenesis during embryonic development. They regulate cell proliferation, survival, migration, and stemness; consequently, they are involved in various human genetic disorders and cancer. SALL4 is a well-recognized oncogene; however, SALL1–3 play dual roles depending on the cancer context and stage of the disease.
  • 1.1K
  • 11 Jan 2022
Topic Review
Chronic Myeloid Neoplasms
Chronic myeloid neoplasms are clonal diseases with variable clinical course and outcomes and despite the introduction of novel therapies, patients with high-risk disease continue to have overall poor outcomes. 
  • 1.1K
  • 29 Apr 2021
Topic Review
Mathematical Modeling of Tumor Vasculature/Angiogenesis
The recruitment of new vasculature via angiogenesis is a critical component of tumor development, which fundamentally influences tumor growth and response to treatment. The characterization of tumor-induced angiogenesis via mathematical models could enable approaches to forecast tumor response and improve patient care.
  • 1.1K
  • 23 Jul 2021
Topic Review
Stability of CD39+CD103+CD8+ T Cells
Tumor-infiltrating CD8+ T cells (TIL) are of the utmost importance in anti-tumor immunity. CD103 defines tumor-resident memory T cells (TRM cells) associated with improved survival and response to immune checkpoint blockade (ICB) across human tumors. Co-expression of CD39 and CD103 marks tumor-specific TRM with enhanced cytolytic potential, suggesting that CD39+CD103+ TRM could be a suitable biomarker for immunotherapy. However, little is known about the transcriptional activity of TRM cells in situ. We analyzed CD39+CD103+ TRM cells sorted from human high-grade endometrial cancers (n = 3) using mRNA sequencing. Cells remained untreated or were incubated with PMA/ionomycin (activation), actinomycin D (a platinum-like chemotherapeutic that inhibits transcription), or a combination of the two. Resting CD39+CD103+ TRM cells were transcriptionally active and expressed a characteristic TRM signature. Activated CD39+CD103+ TRM cells differentially expressed PLEK, TWNK, and FOS, and cytokine genes IFNG, TNF, IL2, CSF2 (GM-CSF), and IL21. Findings were confirmed using qPCR and cytokine production was validated by flow cytometry of cytotoxic TIL. We studied transcript stability and found that PMA-responsive genes and mitochondrial genes were particularly stable. In conclusion, CD39+CD103+ TRM cells are transcriptionally active TRM cells with a polyfunctional, reactivation-responsive repertoire. Secondly, we hypothesize that differential regulation of transcript stability potentiates rapid responses upon TRM reactivation in tumors.
  • 1.1K
  • 03 Nov 2020
Topic Review
Intertumoural and Intratumoural Heterogeneity in Melanoma
Tumour heterogeneity is a phenomenon where the cancer cells evolve diversely over the course of the disease. As a result of the evolution, the cancer cells can be found to be genetically, epigenetically and/or phenotypically different in order to survive in the human body. The tumour microenvironment also plays a crucial role during the evolution.
  • 1.0K
  • 01 Jul 2022
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