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Topic Review
Mitochondrial Metabolism
Energy is needed by cancer cells to stay alive and communicate with their surroundings. The primary organelles for cellular metabolism and energy synthesis are mitochondria. Researchers recently proved that cancer cells can steal immune cells’ mitochondria using nanoscale tubes. This finding demonstrates the dependence of cancer cells on normal cells for their living and function. It also denotes the importance of mitochondria in cancer cells’ biology. Emerging evidence has demonstrated how mitochondria are essential for cancer cells to survive in the harsh tumor microenvironments, evade the immune system, obtain more aggressive features, and resist treatments. For instance, functional mitochondria can improve cancer resistance against radiotherapy by scavenging the released reactive oxygen species. Therefore, targeting mitochondria can potentially enhance oncological outcomes, according to this notion. The tumors’ responses to anticancer treatments vary, ranging from a complete response to even cancer progression during treatment. Therefore, personalized cancer treatment is of crucial importance. So far, personalized cancer treatment has been based on genomic analysis. Evidence shows that tumors with high mitochondrial content are more resistant to treatment.
  • 546
  • 21 Aug 2023
Topic Review
Oral Mucositis in Cancer
Oral mucositis (OM) is a pathological condition with several oral manifestations, originate from cytotoxic effects of non-surgical cancer therapies. The clinical manifestation ranges from diffuse erythematous areas to necrotic ulcers lesions in the mucosa. The oral mucosa presents confluent, deep, and devastatingly painful ulcerations in the most advanced clinical form. Almost all oral or oropharyngeal mucosa areas undergoing radiation will develop this side effect, however, the patients undergoing chemotherapy regiment develop the condition depending on the dose and cytotoxicity of the drug used. Usually, incidence goes around 20 to 40% for solid tumors, while in the therapies with a high dose of cytotoxic drugs, like hematopoietic stem cell transplant, the incidence is around 80%. The patients that develop OM during the cancer treatment can manifest alterations in physical, mental, emotional, and social health factors, proving an unhealthy state. Patients present diet modifications and weight loss, necessitate opioid analgesics, require supplemental nutrition, increase the risk of bacteremia and sepsis, disrupt optimal cancer therapy, and increase healthcare costs. It is common the association of head and neck cancer and OM in medical care however, the frequency in other cancers has long been overlooked and underreported.  For this reason, a multidisciplinary team composed of other health professionals, as dentists, can identify and treat pathologies in advance during oncological treatment. The OM development is described in a five-step pathogenesis model with several biological factors’ combinations. The lesion occurs with the damage of basal epithelial cells due to the radio-chemotherapy. The cascade of events starts with severe alterations in the environment that involves the generation of reactive oxygen species (ROS), activation of transcription factors (NF-kB) and inflammatory pathways (COX), and up-regulation of proinflammatory cytokines (TNF-a, IL1b, and IL-6). The clinical diagnosis can be made in the early stages. The mucosa presents erythema, the patients complain of burning and intolerance of some specific foods. After two weeks, the ulcerated lesions can be detected in one or more areas of the oral cavity. The patient refers to slight discomfort and inconvenience to severe pain, dysphagia, and difficulty in eating that lead to the opioid intervention. As a result of the cancer treatment, it is common to occur salivary alterations in composition and quantity, leading to the exasperation of OM development and impairment in the patient’s quality of life. The lesions recover depending on the patient's immune compromise, however, heal spontaneously for at least 2 weeks following the completion of the therapeutic regimen. Medical and scientific community discourse about effective management of OM in cancer patients due to its high incidence and clinical significance in patient prognosis. Several scientific studies are carried out to discover a well-defined strategy that provides improved management of OM that may allow more aggressive therapeutic doses and more effective cancer treatment, improved patient survival, and wellbeing. All guidelines for the management of OM agree OM management can be divided into three basic components: general oral care, prevention, and palliative cares. The oral care purpose is to reduce some host-related risk factors for stomatitis, including lowering the impact of oral microbial flora. Therefore, a simple care protocol must be suggested, as brushing teeth, daily flossing, and mouth rinsing. In addition, spicy food, alcoholic beverages, and alcohol-based mouthwashes must be avoided. Prevention is the second most important factor in addressing oral mucositis. The combination of agents and physical strategies can provide anti-inflammatory, analgesic, and anti-microbial more effective effects in OM management. The preventive use of oral cryotherapy and photobiomodulation (PBM) therapy showed a reduction in the impact of the treatment toxicity in the oral mucosa. The OM treatment effectivity increase can be noted with the use of several pharmacological agents (pentoxifylline, benzydamine hydrochloride, thalidomide, and simvastatin) and natural products such as Omega-3 FFA, essential oils from manuka (Leptospermum scoparium), vitamins, glutamine, chamomile, aloe vera, and curcumin. The OM palliative care has focused on symptom control using topical or systemic analgesics and the application of barrier agents to cover injured mucosa. In conclusion, OM is a painful and wasting consequence of anticancer chemotherapy and/or radiotherapy.  The occurrence of this pathology increases the risk of treatment interruption and a decrease in quality of life. A multidisciplinary team can provide global attention during the treatment, detecting early necessary interventions to manage the side effects of the cytotoxic therapeutic and providing wellbeing for cancer patients.
  • 545
  • 29 Mar 2022
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.
  • 545
  • 15 Nov 2021
Topic Review
Transcriptional Regulation of Wnt/β-Catenin Pathway in Colorectal Cancer
The Wnt/β-catenin signaling pathway exerts integral roles in embryogenesis and adult homeostasis. Aberrant activation of the pathway is implicated in growth-associated diseases and cancers, especially as a key driver in the initiation and progression of colorectal cancer (CRC). 
  • 545
  • 14 Oct 2022
Topic Review
ERα36 in the Landscape of ERα Variants
Estrogen nuclear receptors, represented by the canonical forms ERα66 and ERβ1, are the main mediators of the estrogen-dependent pathophysiology in mammals. However, numerous isoforms have been identified, stimulating unconventional estrogen response pathways leading to complex cellular and tissue responses. The estrogen receptor variant, ERα36, was cloned in 2005 and is mainly described in the literature to be involved in the progression of mammary tumors and in the acquired resistance to anti-estrogen drugs, such as tamoxifen. Nevertheless, recent data specify the place that ERα36 currently occupies within the diversity of nuclear and membrane estrogen receptors and highlight the impact of ERα36 expression and/or activity in normal breast and testicular cells, but also in different types of tumors including mammary tumors. Therefore, ERα36 can now be considered as a marker of malignancy and the regulation of ERα36 expression could provide new clues to counteract resistance to cancer treatments in hormone-sensitive tumors.
  • 544
  • 17 Jun 2020
Topic Review
Biomarkers in urothelial cancer
The prognosis and responsiveness to chemotherapy and checkpoint inhibitors differs substantially among patients with bladder cancer (BC). There is an unmet need for biomarkers that can accurately predict prognosis and treatment outcome. Here, we describe the available literature on the prognostic and predictive value of tumor-infiltrating immune cells in BC. Current evidence indicates that a high density of tumor-infiltrating CD8+ T cells is a favorable prognostic factor, whereas PD-L1 expression and tumor-associated macrophages are unfavorable prognostic features. While PD-L1 expression appears unsuccessful as biomarker for response to checkpoint inhibitors, there are some indications that high CD8+ T cell infiltration, low transforming growth factor-beta signaling and low densities of myeloid-derived suppressor cells are associated with response. Future studies should focus on combinations of biomarkers to accurately predict survival and response to treatment.
  • 544
  • 12 Oct 2020
Topic Review
MicroRNA in Epstein–Barr Virus-Associated Cancers
A conservative estimate suggests that almost 1.4 million of malignancies are associated with oncogenic viruses, including the hepatitis B virus, hepatitis C virus, Kaposi sarcoma-associated herpesvirus, human T lymphotropic virus type 1, human papillomaviruses, and Epstein–Barr virus (EBV). The oncogenic properties of these viruses are directly related to their ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion. Among these viruses, EBV, formerly designated as the human herpesvirus type 4 (HHV-4), is a y-herpesvirus containing a linear, double-stranded DNA genome of ~172 kilobase pairs (kbp), encoding nearly 80 proteins and 46 functional small untranslated RNAs. The genetic material of EBV is enclosed in an icosahedral nucleocapsid surrounded by the viral tegument and lipid-containing outer envelope. EBV is transmitted through oral contact, particularly in the early years of life, usually without causing disease. EBV can also be transmitted through organ transplantation and blood transfusion. The life cycle of EBV primarily involves the infection of lymphocytes and potentially epithelial cells. Although EBV often exists as an asymptomatic infection, it is involved in the development of about 1.5% of all cancers worldwide. In fact, EBV was the first virus to have been directly associated with cancer in humans. EBV-associated neoplasms affect both immune-competent and immunocompromised hosts, including, for example, some organ transplant recipients. Immune dysregulation and genetic susceptibility are probable co-factors in most, if not all, EBV-associated cancers.
  • 544
  • 22 Sep 2021
Topic Review
Therapeutic Strategies Targeting IDH-Mutations
Mutations of isocitrate dehydrogenase (IDH) genes are the distinctive genetic feature of lower-grade gliomas (LGGs). Tumor-associated IDH1/2 mutations result in a loss of normal enzymatic function and the abnormal production of 2-hydroxyglutarate (2-HG), which acts as an oncometabolite causing widespread changes in histone and DNA methylation and altering cellular metabolism. The “truncal” role of IDH mutations in gliomagenesis  is examined here, giving hints on the different therapeutic strategies targeting IDH1/2-mutated gliomas.
  • 544
  • 07 Mar 2022
Topic Review
Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer
Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%.
  • 544
  • 21 Sep 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. 
  • 544
  • 22 Sep 2022
Topic Review
Matrix Metalloproteinases Inhibitors in Cancer Treatment
Matrix metalloproteinases (MMPs) are a member of the enzyme group that is capable of protein degradation. MMPs are recognized as metalloproteinases because they require either zinc and calcium to perform their functions.
  • 544
  • 25 Jul 2023
Topic Review
Protein SUMOylation in Human Hepatocellular Carcinoma
Small ubiquitin-like modifier (SUMO) is a highly conserved post-translational modification protein, mainly found in eukaryotes. They are widely expressed in different tissues, including the liver. As an essential post-translational modification, SUMOylation is involved in many necessary regulations in cells. It plays a vital role in DNA repair, transcription regulation, protein stability and cell cycle progression. Increasing shreds of evidence show that SUMOylation is closely related to Hepatocellular carcinoma (HCC). 
  • 543
  • 15 Nov 2021
Topic Review
Cancer Treatment and Immunotherapy during Pregnancy
According to McCormik and Peterson (2018), the most common cancers of reproductive age in women are melanoma, breast cancer (the most common gestational cancer and reaches 20% of cases), thyroid cancer, cervical cancer, and lymphomas (most commonly Hodgkin’s lymphoma). A pregnancy that coexists with cancer is not an ordinary pregnancy and consists of a complex medical condition. In the majority of these cases, various therapeutic and ethical dilemmas arise.
  • 543
  • 21 Oct 2022
Topic Review
Manipulating EVs for Therapeutic Applications
Extracellular vesicles (EVs) receive special attention from clinicians due to their assumed usefulness as prognostic markers, immune modulators and physiological delivery tools. The latter application, that supports the reduction of side effects of treatment, is still fraught with many challenges, including established methods for loading EVs with selected cargo and directing them towards target cells. EVs could be loaded with selected cargo either in vitro using several physicochemical techniques, or in vivo by modification of parental cell. Otherwise, EVs may be passively supplemented with selected cargo, such as miRNAs or siRNA. Furthermore, recent findings imply that antigen-specific antibody light chains could coat the surface of EVs to increase the specificity of cell targeting. In addition, the route of EVs’ administration also determines their bioavailability and eventually induced therapeutic effect.
  • 542
  • 03 Jul 2020
Topic Review
Anti-PD-1/PD-L1 Therapy for Bladder Cancer
In high-risk non-muscle invasive bladder cancer (HR-NMIBC), patient outcome is negatively affected by lack of response to Bacillus-Calmette Guérin (BCG) treatment. Lack of response to cisplatin-based neoadjuvant chemotherapy and cisplatin ineligibility reduces successful treatment outcomes in muscle-invasive bladder cancer (MIBC) patients. The effectiveness of PD-1/PD-L1 immune checkpoint inhibitors (ICI) in metastatic disease has stimulated its evaluation as a treatment option in HR-NMIBC and MIBC patients. However, the observed responses, immune-related adverse events and high costs associated with ICI have provided impetus for the development of methods to improve patient stratification, enhance anti-tumorigenic effects and reduce toxicity.
  • 542
  • 24 Mar 2021
Topic Review
Immunotherapy in Hepatobiliary Cancers
Hepatobiliary cancers, including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder carcinoma (GBC), are lethal cancers with limited therapeutic options. Curative-intent treatment typically involves surgery, yet recurrence is common and many patients present with advanced disease not amenable to an operation. Immunotherapy represents a promising approach to improve outcomes, but the immunosuppressive tumor microenvironment of the liver characteristic of hepatobiliary cancers has hampered the development and implementation of this therapeutic approach. Current immunotherapies under investigation include immune checkpoint inhibitors (ICI), the adoptive transfer of immune cells, bispecific antibodies, vaccines, and oncolytic viruses. Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two ICIs that have demonstrated utility in HCC, and newer immune checkpoint targets are being tested in clinical trials.
  • 542
  • 17 Aug 2021
Topic Review
Monoamine Oxidase (MAO) for Anticancer Drug Design
Monoamine oxidases (MAOs) are oxidative enzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Owing to the crucial role of MAOs in maintaining functional levels of neurotransmitters, the implications of its distorted activity have been associated with numerous neurological diseases. Recently, an unanticipated role of MAOs in tumor progression and metastasis has been reported.
  • 542
  • 11 Oct 2021
Topic Review
Oral Microbiota in Chemotherapy-Induced Oral Mucositis in Children
The perturbation of the diversity and proportions of species within the oral microbiota leads to dysbiosis and associated increased risk of local and systemic diseases. In children who receive chemotherapy for cancer, oral mucositis is a common and painful side effect that decreases quality of life (QoL) and treatment adherence. The oral microbiota undergoes a substantial dysbiosis as an effect of cancer and its treatment, characterized by lower richness and less diversity. Furthermore, this dysbiosis seems to promote pro-inflammatory cytokine release and pro-apoptotic mediators, enhancing the oral tissue damage. Further studies on the role of the oral microbiota in the pathogenesis of oral mucositis should be performed among children with cancer who receive chemotherapy, to find preventive and protective factors against the pathogenesis of oral mucositis.
  • 542
  • 18 Apr 2022
Topic Review
Neoantigen-Derived Cancer Vaccines
Cancers are driven by genetic instabilities that rapidly accumulate somatic mutations and eventually alter cell properties. Cancer immunotherapy has achieved multiple clinical benefits and has become an indispensable component of cancer treatment. Targeting tumor-specific antigens, also known as neoantigens, plays a crucial role in cancer immunotherapy. T cells of adaptive immunity that recognize neoantigens, but do not induce unwanted off-target effects, have demonstrated high efficacy and low side effects in cancer immunotherapy. 
  • 542
  • 31 May 2022
Topic Review
Immunotherapy for Cancer
Cancer immunotherapies, such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T cells (CAR-T), have dramatically altered the treatment landscape for many solid and hematologic malignancies. Ongoing research continues to investigate ways to harness the immune system to treat cancer and broaden the indications for currently available therapies. Although immunotherapies have revolutionized the treatment of solid and hematologic malignancies, they have unique toxicity profiles based on their mode of action. Despite this, such innovative therapies can potentially increase already-in-use therapies’ effectiveness.
  • 542
  • 14 Oct 2022
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