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Topic Review
HER2 Status in the Biliary Tract Cancers
Biliary tract cancer (BTC) is traditionally known as being hard to treat with a poor prognosis. State-of-the-art genomic technologies such as next-generation sequencing (NGS) revolutionized cancer management and shed light on the genomic landscape of BTCs. There are ongoing clinical trials to assess the efficacy of HER2-blocking antibodies or drug conjugates in BTCs with HER2 amplifications. 
  • 981
  • 10 May 2023
Topic Review
Online Adaptive Radiotherapy in Treating Gynecologic Cancers
Online adaptive radiation is a new and exciting modality of treatment for gynecologic cancers. Traditional radiation treatments deliver the same radiation plan to cancers with large margins. Improvements in imaging, technology, and artificial intelligence have made it possible to account for changes between treatments and improve the delivery of radiation. These advances can potentially lead to significant benefits in tumor coverage and normal tissue sparing. Gynecologic cancers can uniquely benefit from this technology due to the significant changes in bladder, bowel, and rectum between treatments as well as the changes in tumors commonly seen between treatments. Preliminary studies have shown that online adaptive radiation can maintain coverage of the tumor while sparing nearby organs. 
  • 981
  • 27 Feb 2023
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. 
  • 980
  • 28 Apr 2021
Topic Review
P53 Dysfunction in Colorectal Cancer
Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g., KRAS) and inactivation of tumor suppression genes, namely TP53 and APC, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the TP53 gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling.
  • 980
  • 23 Jun 2021
Topic Review
Proteomic Research on Antitumor Properties of Medicinal Mushrooms
Medicinal mushrooms are increasingly being recognized as an important therapeutic modality in complementary oncology. Until now, more than 800 mushroom species have been known to possess significant pharmacological properties, of which antitumor and immunomodulatory properties have been the most researched. Besides a number of medicinal mushroom preparations being used as dietary supplements and nutraceuticals, several isolates from mushrooms have been used as official antitumor drugs in clinical settings for several decades. Various proteomic approaches allow for the identification of a large number of differentially regulated proteins serendipitously, thereby providing an important platform for a discovery of new potential therapeutic targets and approaches as well as biomarkers of malignant disease. This entry is focused on the current state of proteomic research into antitumor mechanisms of some of the most researched medicinal mushroom species, including Phellinus linteus, Ganoderma lucidum, Auricularia auricula, Agrocybe aegerita, Grifola frondosa, and Lentinus edodes, as whole body extracts or various isolates, as well as of complex extract mixtures.
  • 980
  • 15 Nov 2021
Topic Review
Protein Palmitoylation in Tumor Cell Deaths
Researchers delve into the multifaceted role of palmitoylation across various cell death modalities in the oncological context, from its intricate correlations with tumorigenesis, steered by the Asp-His-His-Cys tetrapeptide motif (DHHC) family, to the counter-process of depalmitoylation mediated by enzymes like Palmitoyl protein thioesterase-1 (PPT1).
  • 980
  • 29 Nov 2023
Topic Review
Metabolic Heterogeneity of Cancer Cells
It has been long recognized that cancer cells reprogram their metabolism under hypoxia conditions due to a shift from oxidative phosphorylation (OXPHOS) to glycolysis in order to meet elevated requirements in energy and nutrients for proliferation, migration, and survival. However, data accumulated over recent years has increasingly provided evidence that cancer cells can revert from glycolysis to OXPHOS and maintain both reprogrammed and oxidative metabolism, even in the same tumor. This phenomenon, denoted as cancer cell metabolic plasticity or hybrid metabolism, depends on a tumor micro-environment that is highly heterogeneous and influenced by an intensity of vasculature and blood flow, oxygen concentration, and nutrient and energy supply, and requires regulatory interplay between multiple oncogenes, transcription factors, growth factors, and reactive oxygen species (ROS), among others. Hypoxia-inducible factor-1 (HIF-1) and AMP-activated protein kinase (AMPK) are key modulators of the switch between reprogrammed and oxidative metabolism. Our review focuses on cross-talks between HIF-1, glucose transporters (GLUTs), and AMPK, and other regulatory proteins including oncogenes such as c-Myc, p53, and KRAS along with growth factor-initiated protein kinase B (PKB)/Akt, phosphatidyl-3-kinase (PI3K), and mTOR signaling pathways in controlling cancer cell metabolism.
  • 979
  • 23 Jun 2021
Topic Review
Biomarker for Thyroid Cancer
Thyroid cancer has the most rapidly increasing incidence rate among all major cancers, with a triple increase from 4.5 to 14.4 per 100,000 population during 1974–2013. It was estimated 52,890 new cases in the United States in 2020 and contributed to 0.36% of all cancer deaths. Most primary thyroid cancers are follicular cell-derived epithelial tumors, making up four main pathological carcinoma types: papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC).
  • 979
  • 29 Mar 2022
Topic Review
GPR56 a Novel Immune Checkpoint on Tumor-Infiltrating Lymphocytes
Despite the clinical efficacy of so-called immune checkpoint inhibitors (ICIs) in various cancers, some cancer types, including epithelial ovarian cancer (EOC), do not effectively respond to current therapeutics. Thus, the identification of new immune checkpoints that regulate T cell immunity remains of great interest. One as yet largely uninvestigated checkpoint of potential interest is the G protein-coupled receptor 56 (GPR56), which belongs to the adhesion GPCR family. Here in this study,   it was identified that GPR56 is expressed on tumor infiltrating lymphocytes (TILs) and investigated its role as a potential immune checkpoint within the context of cancer. Based on the investigated data, GPR56 indeed appears to function as an immune checkpoint in TILs and may thus provide a novel immunotherapeutic target for the reactivation of tumor-infiltrating and tumor-reactive lymphocytes.
  • 979
  • 22 Nov 2022
Topic Review
Neoadjuvant treatment in breast cancer
Neoadjuvant Chemotherapy (NAC) in Breast Cancer (BC) has proved useful for the reduction in tumor burden prior to surgery, allowing for a more extensive breast preservation and the eradication of subjacent micrometastases. However, the impact on prognosis is highly dependent on the establishment of Pathological Complete Response (pCR), in particular for Triple Negative (TN) and Hormonal Receptor negative/Human Epidermal growth factor Receptor 2 positive (HR−/HER2+) subtypes. Several pCR predictors, such as PAM50, Integrative Cluster (IntClust), mutations in PI3KCA, or the Trastuzumab Risk model (TRAR), are useful molecular tools for estimating response to treatment and are prognostic. Major evolution events during BC NAC that feature the Residual Disease (RD) are the loss of HR and HER2, which are prognostic of bad outcome, and stemness and immune depletion-related gene expression aberrations. This dynamic nature of the determinants of response to BC NAC, together with the extensive heterogeneity of BC, raises the need to discern the individual and subtype-specific determinants of resistance. Moreover, refining the current approaches for a comprehensive monitoring of tumor evolution during treatment, RD, and eventual recurrences is essential for identifying new actionable alterations and the integral best management of the disease.breast cancer; neoadjuvant chemotherapy; pathological complete response; predictive markers; residual diseasebreast cancer; neoadjuvant chemotherapy; pathological complete response; predictive markers; residual disease
  • 978
  • 08 Aug 2020
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.
  • 978
  • 11 Apr 2022
Topic Review
Cancer Associated Fibroblasts
Cancer-associated fibroblasts are important players of the tumour microenvironment. They influence numerous processes during tumour development and progression, including the response of cancer cells to treatment. As a consequence, this cell type has emerged has a prominent target in anti-cancer therapy.
  • 977
  • 28 Jul 2021
Topic Review
Neuroendocrine Tumors
Neuroendocrine neoplasms (NENs) first described as “karzinoide” by Dr. Oberndorfer in 1907, comprise a family of heterogeneous tumors which can range from well differentiated neuroendocrine tumors (NETs) to poorly differentiated neuroendocrine carcinomas (NECs). NENs emerge from the diffuse endocrine systemand therefore can be found throughout the body, but they most commonly occur in the gastrointestinal tract with a peak incidence around the 5th and 6th decade of life. Based on the latest Survival Epidemiology and End Results data, incidence of NENs is on the rise with almost 7 cases per 100,000 persons in the United States. NENs can be alternatively classified as functional or non-functional based on the release of specific hormones by the tumor cells (e.g., serotonin, vasoactive intestinal peptide, insulin, gastrin, somatostatin, glucagon) and the subsequent development of various secretory syndromes.
  • 977
  • 16 Dec 2021
Topic Review
Protein Kinase C in NSCLC
Despite significant advances, targeted therapy is greatly limited by resistance acquisition, which emerges in nearly all patients receiving treatment. As a result, identifying the molecular modulators of resistance is of great interest. Recent work has implicated protein kinase C (PKC) isozymes as mediators of drug resistance in non-small cell lung cancer (NSCLC). Importantly, previous findings on PKC have implicated this family of enzymes in both tumor-promotive and tumor-suppressive biology in various tissues. Here, we review the biological role of PKC isozymes in NSCLC through extensive analysis of cell-line-based studies to better understand the rationale for PKC inhibition.
  • 976
  • 22 Sep 2021
Topic Review
Metabolism-Associated Epigenetic and Immunoepigenetic Re-programming in Liver Cancer
Metabolic reprogramming and epigenetic changes have been characterized as hallmarks of liver cancer. Metabolic intermediates serve as crucial substrates for various epigenetic modulations, from post-translational modification of histones to DNA methylation. In turn, epigenetic changes can alter the expression of metabolic genes supporting on the one hand, the increased energetic demand of cancer cells and, on the other hand, influence the activity of tumor-associated immune cell populations. In this review, we will illustrate the most recent findings about metabolic reprogramming in liver cancer. We will focus on the metabolic changes characterizing the tumor microenvironment and on how these alterations impact on epigenetic mechanisms involved in the malignant progression. Furthermore, we will report our current knowledge about the influence of cancer-specific metabolites on epigenetic reprogramming of immune cells. Finally, we will review the current strategies to target metabolic and epigenetic pathways and their therapeutic potential in liver cancer, alone or in combinatorial approaches.
  • 976
  • 13 Dec 2021
Topic Review
Breast Cancer-Associated Fibroblasts
Breast cancer-associated fibroblasts (BCAFs) are the CAFs present in breast cancers with genetic and phenotypic characteristics similar to CAFs. CAFs originate from a diverse range of cells, including endothelial cells, adipocytes, pericytes, and MSCs. Although CAFs were derived from endothelial cells and pericytes, the derivation was not tested in breast cancer models similar to other cancers. BCAFs have also been derived from adipocytes that lead to a desmoplastic microenvironment. BCAFs can originate from MSCs, which contribute to angiogenesis through up-regulation of clusterin leading to tumorigenesis. BCAFs possess the fibrillar collagen receptor, DDR2, which rearranges collagen fibers to develop an invasive and metastatic TME. Additionally, integrin α11 in BCAFs interacts with platelet-derived growth factor receptor beta (PDGFRβ) and promotes invasiveness by activating c-Jun N-terminal kinase (JNK) and producing a matricellular protein, tenascin C.
  • 976
  • 14 Jan 2022
Topic Review
C-Terminal CPE in Brain Metastasis from Breast Cancer
Brain metastasis occurs in primary cancers, such as breast cancer, and is correlated with mortality. There are limited options available for treatment, but Clostridium perfringens Enterotoxin (CPE) and its interaction with Claudin-4, a possible diagnostic biomarker for breast cancer, can provide a molecular pathway basis for the development of treatment options for metastatic brain cancer. 
  • 976
  • 22 Sep 2022
Topic Review
Cholesterol Biosynthesis and Breast Cancer Initiation and Development
Cholesterol (CHOL) is a multifaceted lipid molecule. It is an essential structural component of cell membranes, where it cooperates in regulating the intracellular trafficking and signaling pathways. Additionally, it serves as a precursor for vital biomolecules, including steroid hormones, isoprenoids, vitamin D, and bile acids. Although CHOL is normally uptaken from the bloodstream, cells can synthesize it de novo in response to an increased requirement due to physiological tissue remodeling or abnormal proliferation, such as in cancer. Cumulating evidence indicated that increased CHOL biosynthesis is a common feature of breast cancer and is associated with the neoplastic transformation of normal mammary epithelial cells.
  • 976
  • 29 Feb 2024
Topic Review
Surgical Approaches to Neuroblastoma
Neuroblastoma (NB) is the most commonly occurring soft-tissue malignancy of childhood. Surgery plays an important role in multidisciplinary treatment and its principal aim is a local control of the disease, respecting the integrity of the surrounding structures. There is no unanimous consensus on the best surgical technique, and the operative approach largely depends on the anatomical location and the extension of the mass. To have a complete overview of the different type of treatment, we made a review of the literature from the last twenty years of all the surgical approaches applied for NBs resection, accordingly to the anatomical site.
  • 975
  • 23 Jun 2021
Topic Review
ADGRG1/GPR56 in Tumor Progression
Cellular communication plays a critical role in diverse aspects of tumorigenesis including tumor cell growth/death, adhesion/detachment, migration/invasion, angiogenesis, and metastasis. G protein-coupled receptors (GPCRs) which constitute the largest group of cell surface receptors are known to play fundamental roles in all these processes. When considering the importance of GPCRs in tumorigenesis, the adhesion GPCRs (aGPCRs) are unique due to their hybrid structural organization of a long extracellular cell-adhesive domain and a seven-transmembrane signaling domain. Indeed, aGPCRs have been increasingly shown to be associated with tumor development by participating in tumor cell interaction and signaling. ADGRG1/GPR56, a representative tumor-associated aGPCR, is recognized as a potential biomarker/prognostic factor of specific cancer types with both tumor-suppressive and tumor-promoting functions. 
  • 975
  • 16 Dec 2021
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