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Topic Review
Triple-Negative Breast Cancer and Other Breast Cancer
Due to the need for quality biomarkers for triple-negative breast cancer (TNBC) because of its aggressive nature and limited therapeutic options, it is not surprising that several studies have focused on identifying expression differences in peripheral blood cells between TNBC patients and other classical breast cancer (BC) subtypes. 
  • 686
  • 13 Apr 2022
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.
  • 685
  • 03 Nov 2020
Topic Review
Caveolin-1 in Lung Cancer
Lung cancer is one of the most common and malignant cancers with extremely high morbidity and mortality in both males and females. Although traditional lung cancer treatments are fast progressing, there are still limitations. Caveolin-1 (Cav-1), a main component of caveolae, participates in multiple cellular events such as immune responses, endocytosis, membrane trafficking, cellular signaling and cancer progression. It has been found tightly associated with lung cancer cell proliferation, migration, apoptosis resistance and drug resistance. In addition to this, multiple bioactive molecules have been confirmed to target Cav-1 to carry on their anti-tumor functions in lung cancers. Cav-1 can also be a predictor for lung cancer patients’ prognosis. 
  • 685
  • 22 Sep 2021
Topic Review
Alcohol and Head and Neck Cancer
As suggested from recent findings, the role of alcohol in HNC seems to be broader than that of a simple risk factor. In this entry, authors report evidence from past studies to clarify the role of alcohol consumption in head and neck cancer (HNC) onset. Moreover, we further explore the role of oral microbiota, oxidative stress and genetic expression alterations due to alcohol drinking. Although alcohol is not the exclusive risk factor for HNC carcinogenesis, it plays a major role in the etiopathogenesis of both primary tumors and their recurrences, especially by means of ethanol and its metabolic products. Alcohol modifies oral microbiota, enhances intracellular oxidative stress, expose epithelial cells to carcinogens and alters cellular genetic expressions by promoting epigenetic mutations, DNA damage, and inaccurate DNA repair related to the formation of DNA adducts. The relationship between alcohol and HNC has been well established but, unfortunately, there is no clear threshold effect of alcohol for oncogenic patients, so that prevention and monitoring with long-term markers of alcohol consumption (especially those detected in the hair) that relay information on the actual alcohol drinking habits, seem to be the most effective ways to contrast its prevalence (and complications) in HNC drinker-patients. These conclusions seem to be especially important nowadays since, despite the established association between alcohol and HNC, a concerning pattern of alcohol consumption misconducts has been found in both in the general population and HNC  survivors. Interestingly, evidence that we report on HNC etiopathogenesis suggests a key role of polyphenols and alkylating agents for patient management, especially in case of heavy chronic drinkers.
  • 685
  • 20 Jan 2022
Topic Review
Platinum Resistance in Ovarian Cancer
Ovarian cancer is the most lethal gynecologic malignancy. Platinum-based chemotherapy is the backbone of treatment for ovarian cancer, and although the majority of patients initially have a platinum-sensitive disease, through multiple recurrences, they will acquire resistance. Platinum-resistant recurrent ovarian cancer has a poor prognosis and few treatment options with limited efficacy. Resistance to platinum compounds is a complex process involving multiple mechanisms pertaining not only to the tumoral cell but also to the tumoral microenvironment. 
  • 685
  • 23 Mar 2023
Topic Review
ADT for castration-resistant prostate cancer
The androgen receptor (AR) is one of the main components in the development and progression of prostate cancer (PCa), and treatment strategies are mostly directed toward manipulation of the AR pathway. In the metastatic setting, androgen deprivation therapy (ADT) is the foundation of treatment in patients with hormone-sensitive prostate cancer (HSPC). However, treatment response is short-lived, and the majority of patients ultimately progress to castration-resistant prostate cancer (CRPC). 
  • 684
  • 08 Apr 2021
Topic Review
Putative Anticancer Compounds from Plant-Derived Endophytic Fungi
Endophytic fungi are microorganisms that exist almost ubiquitously inside the various tissues of living plants where they act as an important reservoir of diverse bioactive compounds. Recently, endophytic fungi have drawn tremendous attention from researchers; their isolation, culture, purification, and characterization have revealed the presence of around 200 important and diverse compounds including anticancer agents, antibiotics, antifungals, antivirals, immunosuppressants, and antimycotics. Many of these anticancer compounds, such as paclitaxel, camptothecin, vinblastine, vincristine, podophyllotoxin, and their derivatives, are currently being used clinically for the treatment of various cancers (e.g., ovarian, breast, prostate, lung cancers, and leukemias). By increasing the yield of specific compounds with genetic engineering and other biotechnologies, endophytic fungi could be a promising, prolific source of anticancer drugs. In the future, compounds derived from endophytic fungi could increase treatment availability and cost effectiveness. 
  • 684
  • 17 Jan 2022
Topic Review
Microbiome and Resistance to Chemotherapy
Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. Importantly, preclinical models and clinical studies highlight the critical role of the microbiome in the efficacy of cancer treatment.
  • 683
  • 20 Dec 2022
Topic Review
NRF2 Pathway
The NRF2 pathway represents one of the most intriguing pathways that promotes chemo- and radioresistance of neoplastic cells. Increasing findings suggest that the NRF2 signaling can be modulated by multiple epigenetic factors such as noncoding RNAs, which influence a large number of oncogenic mechanisms, both at transcriptional and at post-transcriptional levels. As a consequence, the identification and characterization of specific noncoding RNAs as biomarkers related to oxidative stress may help to clarify the relationship between them and NRF2 signaling in the tumor context, in terms of positive and negative modulation, also referring to their intersection with other NRF2 crosstalking pathways.
  • 682
  • 18 Dec 2020
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.
  • 682
  • 07 Jun 2021
Topic Review
Escherichiacoli Nissle 1917
Escherichia coli Nissle 1917 (EcN) is a commonly used probiotic in clinical practice. Its facultative anaerobic property drives it to selectively colonize in the hypoxic area of the tumor for survival and reproduction. EcN can be engineered as a bacteria-based microrobot for molecular imaging, drug delivery, and gene delivery.
  • 682
  • 27 Aug 2021
Topic Review
Heat Shock Protein 70 Inhibitors
A class of chaperones dubbed heat shock protein 70 (Hsp70) possesses high relevance in cancer diseases due to its cooperative activity with the well-established anticancer target Hsp90. However, Hsp70 is closely connected with a smaller heat shock protein, Hsp40, forming a formidable Hsp70-Hsp40 axis in various cancers, which serves as a suitable target for anticancer drug design. 
  • 682
  • 27 Feb 2023
Topic Review
RANKL/RANK Axis
Receptor activator of nuclear factor -κΒ (RANK) and the RANK ligand (RANKL) was first reported in the regulation of osteoclast differentiation/activation and bone homeostasis. Additionally, the RANKL/RANK system is a significant mediator of progesterone-driven mammary epithelial cell proliferation, potentially contributing to breast cancer initiation and progression. Moreover , several studies supported a synergistic effect of RANK and epidermal growth factor receptor (EGFR) and described the RANK's involvement in epidermal growth factor receptor 2 (ERBB2) positive carcinogenesis. Consequently, anti-RANKL treatment has been proposed as a new approach to preventing and treating breast cancer and metastases.
  • 681
  • 17 Nov 2020
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. 
  • 681
  • 18 Oct 2022
Topic Review
Pancreatic Enzyme Replacement Therapy
Pancreatic cancer is an aggressive malignancy and the seventh leading cause of global cancer deaths in industrialised countries. More than 80% of patients suffer from significant weight loss at diagnosis and over time tend to develop severe cachexia. A major cause of weight loss is malnutrition. Patients may experience pancreatic exocrine insufficiency (PEI) before diagnosis, during nonsurgical treatment, and/or following surgery. PEI is difficult to diagnose because testing is cumbersome. Consequently, PEI is often detected clinically, especially in non-specialised centres, and treated empirically.
  • 680
  • 25 Jun 2021
Topic Review
Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma
Pancreatic cancer has a complex tumor microenvironment which engages in extensive crosstalk between cancer cells, cancer-associated fibroblasts, and immune cells. Many of these interactions contribute to tumor resistance to anti-cancer therapies. Using targeted drugs to disrupt interactions between these cells which can support cancer cell growth, invasion, and immune suppression has become an important area of exploration in the pancreatic cancer field.  Pancreatic ductal adenocarcinoma (PDAC) is the most common histology of pancreatic cancer, representing >85% of all pancreatic cancer diagnoses.
  • 680
  • 08 Sep 2022
Topic Review
Poly ADP Ribose Polymerase Inhibitors
Poly ADP ribose polymerases (PARPs) are a family of enzymes that catalyse the transfer of ADP-ribose to target proteins, functioning in fundamental cellular processes including transcription, chromatin remodelling and DNA repair. PARP inhibitors (PARPis) including olaparib, niraparib and rucaparib are approved for the clinical management of women with ovarian cancer.
  • 680
  • 12 Oct 2022
Topic Review
Fisetin in Cancer
Fisetin is a flavonoid naturally occurring in various plants that possesses anticancer activity. It has the power to stop cancers from growing quickly, becoming invasive, and spreading to multiple tissues.
  • 680
  • 10 May 2023
Topic Review
Oncolytic Reovirus
Oncolytic virotherapy (OVT) has received significant attention in recent years, especially since the approval of talimogene Laherparepvec (T-VEC) in 2015 by the Food and Drug administration (FDA). Mechanistic studies of oncolytic viruses (OVs) have revealed that most, if not all, OVs induce direct oncolysis and stimulate innate and adaptive anti-tumour immunity. With the advancement of tumour modelling, allowing characterisation of the effects of tumour microenvironment (TME) components and identification of the cellular mechanisms required for cell death (both direct oncolysis and anti-tumour immune responses), it is clear that a “one size fits all” approach is not applicable to all OVs, or indeed the same OV across different tumour types and disease locations. This article will provide an unbiased review of oncolytic reovirus (clinically formulated as pelareorep), including the molecular and cellular requirements for reovirus oncolysis and anti-tumour immunity, reports of pre-clinical efficacy and its overall clinical trajectory. Moreover, as it is now abundantly clear that the true potential of all OVs, including reovirus, will only be reached upon the development of synergistic combination strategies, reovirus combination therapeutics will be discussed, including the limitations and challenges that remain to harness the full potential of this promising therapeutic agent.
  • 679
  • 09 Nov 2020
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. 
  • 679
  • 28 Apr 2021
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