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Topic Review
Macrophages Proliferation in Health and Disease
Macrophages are the most abundant immune cells of the tumor microenvironment (TME) and have multiple important functions in cancer. Macrophages comprise a heterogeneous and functionally versatile population of innate immune cells. Compelling evidence indicate that the high degree of plasticity of macrophages and their ability to self-renew majorly impact tumor progression and resistance to therapy. In addition, the microenvironmental factors largely affect the metabolism of macrophages and may have a major influence on TAMs proliferation and subsets functions. Thus, understanding the signaling pathways regulating TAMs self-renewal capacity may help to identify promising targets for the development of novel anticancer agents.
  • 709
  • 02 Nov 2022
Topic Review
Antibody–Drug Conjugates Approved in Breast Cancer
Antibody–drug conjugates (ADCs), with antibodies targeted against specific antigens linked to cytotoxic payloads, offer the opportunity for a more specific delivery of chemotherapy and other bioactive payloads to minimize side effects. First approved in the setting of HER2+ breast cancer, more recent ADCs have been developed for triple-negative breast cancer (TNBC) and hormone receptor-positive (HR+) breast cancer.
  • 709
  • 28 Feb 2023
Topic Review
PRDM12 in Health and Diseases
PRDM12 is a member of the PRDI-BF1 (positive regulatory domain I-binding factor 1) homologous domain (PRDM)-containing protein family, a subfamily of Kruppel-like zinc finger proteins, controlling key processes in the development of cancer. PRDM12 is expressed in a spatio-temporal manner in neuronal systems where it exerts multiple functions. PRDM12 is essential for the neurogenesis initiation and activation of a cascade of downstream pro-neuronal transcription factors in the nociceptive lineage.
  • 709
  • 12 Nov 2021
Topic Review
Veterinary Antiparasitic to Human Anticancer
Cancer is an extensive disease and the most common cause of morbidity and mortality worldwide. It is characterized by a deregulation of the cell cycle, which primarily results in a progressive loss of control of cellular growth and differentiation. The repurposing of veterinary antiparasitic drugs for the treatment of cancer is gaining traction, as supported by existing literature. A prominent example is the proposal to implement the use of veterinary antiparasitics such as benzimidazole carbamates and halogenated salicylanilides as novel anticancer drugs. These agents have revealed pronounced anti-tumor activities and gained special attention for “double repositioning”, as they are repurposed for different species and diseases simultaneously, acting via different mechanisms depending on their target. As anticancer agents, these compounds employ several mechanisms, including the inhibition of oncogenic signal transduction pathways of mitochondrial respiration and the inhibition of cellular stress responses.
  • 707
  • 29 Apr 2022
Topic Review
Trop-2 as a Therapeutic Target in Breast Cancer
Trop-2 is an exciting, new target for the treatment of breast cancer. Trop-2 is found at high levels in multiple cancers such as prostate, pancreatic, urothelial, lung, and breast cancer. Among different breast cancer subtypes, Trop-2 is most highly expressed in triple negative breast cancer. Drugs that inhibit Trop-2 are now an important treatment option for patients with metastatic triple negative breast cancer, for whom few treatment options exist.
  • 707
  • 07 Dec 2022
Topic Review
COVID-19 Impact on Cancer-Related Care in America
COVID-19 impacted several health services, including cancer-related care. Its implications were significant due to the lapse in hospital resources, compounded by the delays stemming from the economic effects on patients’ jobs and medical coverage. Furthermore, reports suggesting an increased risk for morbidity and mortality from COVID-19 in patients with cancer and those on active cancer treatment caused additional fear and potential delays in seeking medical services.
  • 707
  • 19 Jan 2023
Topic Review
Estrogens and Lung Cancer
Malignant neoplasms are among the most common diseases and are responsible for the majority of deaths in the developed world. In contrast to men, available data show a clear upward trend in the incidence of lung cancer in women, making it almost as prevalent as breast cancer. Women might be more susceptible to the carcinogenic effect of tobacco smoke than men. Furthermore, available data indicate a much more frequent mutation of the tumor suppressor gene-p53 in non-small cell lung cancer (NSCLC) female patients compared to males. Another important factor, however, might lie in the female sex hormones, whose mitogenic or carcinogenic effect is well known. Epidemiologic data show a correlation between hormone replacement therapy (HRT) or oral contraceptives (OCs), and increased mortality rates due to the increased incidence of malignant tumors, including lung cancer. Interestingly, two types of estrogen receptors have been detected in lung cancer cells: ERα and ERβ. The presence of ERα has been detected in tissues and non-small-cell lung carcinoma (NSCLC) cell lines. In contrast, overexpression of ERβ is a prognostic marker in NSCLC.
  • 706
  • 22 Jan 2021
Topic Review
GnRH in Endometrial Cancer
Endometrial cancer (EC) is one of the most common gynecological malignancies. Gonadotropin releasing hormone (GnRH) is a decapeptide first described to be secreted by the hypothalamus to regulate pituitary gonadotropin secretion. In this systematic review, we analyze and summarize the data indicating that most EC express GnRH and its receptor (GnRH-R) as part of an autocrine system regulating proliferation, the cell cycle, and apoptosis. We analyze the available data on the expression and function of GnRH-II, its putative receptor, and its signal transduction. GnRH-I and GnRH-II agonists, and antagonists as well as cytotoxic GnRH-I analogs, have been shown to inhibit proliferation and to induce apoptosis in human EC cell lines in pre-clinical models. Treatment with conventional doses of GnRH-agonists that suppress pituitary gonadotropin secretion and ovarian estrogen production has become part of fertility preserving therapy of early EC or its pre-cancer (atypical endometrial hyperplasia). Conventional doses of GnRH-agonists had marginal activity in advanced or recurrent EC. Higher doses or more potent analogs including GnRH-II antagonists have not yet been used clinically. The cytotoxic GnRH-analog Zoptarelin Doxorubicin has shown encouraging activity in a phase II trial in patients with advanced or recurrent EC, which expressed GnRH-R. In a phase III trial in patients with EC of unknown GnRH-R expression, the cytotoxic GnRH doxorubicin conjugate was not superior to free doxorubicin. Further well-designed clinical trials exploiting the GnRH-system in EC might be useful. 
  • 706
  • 18 Feb 2021
Topic Review
Complementary and Alternative Therapies in Oncology
Cancer is the second leading cause of death worldwide, after cardiovascular diseases. Increasing patients’ awareness and providing easier access to public information result in greater interest in alternative anticancer or unproven supportive therapies. Fear of cancer and limited trust in the treating physician are also important reasons leading patients to seek these methods. Complementary and alternative medicine (CAM), as opposed to evidence-based medicine (EBM), is not grounded in well-designed clinical studies, and thus may not be effective or may even harm patients. Complementary medicine is used in addition to standard medicine, whereas alternative medicine is used in lieu of standard methods. Patients diagnosed with cancer are frequently confused due to the unpredictability of the situation, stress, and fear of the future of themselves and their families. The willingness to actively participate in the therapeutic process may prompt them to seek allegedly effective CAM options. Patients attempt these methods to increase treatment efficacy, alleviate treatment side effects, or improve their physical and mental condition.
  • 706
  • 26 Apr 2022
Topic Review
Oncogenic Tyrosine Phosphatases
Despite a large number of therapeutic options available, malignant melanoma remains a highly fatal disease, especially in its metastatic forms. The oncogenic role of protein tyrosine phosphatases (PTPs) is becoming increasingly clear, paving the way for novel antitumor treatments based on their inhibition. In this review, we present the oncogenic PTPs contributing to melanoma progression and we provide, where available, a description of new inhibitory strategies designed against these enzymes and possibly useful in melanoma treatment. Considering the relevance of the immune infiltrate in supporting melanoma progression, we also focus on the role of PTPs in modulating immune cell activity, identifying interesting therapeutic options that may support the currently applied immunomodulating approaches.
  • 706
  • 13 Oct 2020
Topic Review
Small Bowel Adenocarcinoma
Small bowel adenocarcinoma (SBA) is a rare malignancy, with a rising incidence in recent decades, and accounts for roughly 40% of all cancers of the small bowel. The majority of SBAs arise in the duodenum and are associated with a dismal prognosis. Surgery remains the mainstay of treatment for localized disease, while systemic treatments parallel those used in colorectal cancer (CRC), both in the adjuvant and palliative setting. In fact, owing to the lack of prospective data supporting its optimal management, SBA has historically been treated in the same way as CRC.
  • 706
  • 23 Feb 2022
Topic Review
Recurrent Glioblastoma
Glioblastoma (GBM) is the most aggressive central nervous system (CNS) primary malignancy in adults, with a median age at diagnosis of 65 years.
  • 705
  • 08 Feb 2021
Topic Review
Androgen Signaling in Prostate Cancer
Key preclinical studies over decades suggest prostate cancer cells titrate androgen signaling to optimize growth. Such laboratory-based studies argue that adaptations that allow growth in a low-androgen environment render prostate cancer sensitive to restoration of androgens, especially at supraphysiologic doses. Based on preclinical data, as well as clinical observations, trials employing high-dose testosterone (HDT) therapy have now been conducted. These trials suggest a clinical benefit in cancer response and quality of life in a subset of castration-resistant prostate cancer patients.
  • 705
  • 18 Sep 2021
Topic Review
Protein Variants in Cancer-Related Genes
Large scale genome sequencing allowed the identification of a massive number of genetic variations, whose impact on human health is still unknown. In this entry we analyze, by an in silico-based strategy, the impact of missense variants on cancer-related genes, whose effect on protein stability and function was experimentally determined. We collected a set of 164 variants from 11 proteins to analyze the impact of missense mutations at structural and functional levels, and to assess the performance of state-of-the-art methods (FoldX and Meta-SNP) for predicting protein stability change and pathogenicity. 
  • 705
  • 22 Sep 2021
Topic Review
Development of Anti-Glutaminolysis Drugs
Glutaminolysis has emerged in recent years as an effective therapeutic focus in the treatment of cancer. In order to restrict the proliferation of glutamine-addicted cancer cells, researchers have created various drugs that target different stages in glutamine metabolism.
  • 705
  • 09 Dec 2022
Topic Review
miRNAs in HTLV-1 Induced T Cell Leukemia
Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. 
  • 705
  • 23 May 2022
Topic Review
Modeling Immune Checkpoint Inhibitors
Immune checkpoint inhibitors are revolutionizing the treatment of cancer, but models that accurately predict their efficacy before administering them to humans are badly needed.  This entry presents the application of a microfluidic tumor model that simulates the interactions between immune cells and tumors in a dynamic microenvironment, utilizing real-time imaging and image analytic algorithms to demonstrate excellent correlations between the laboratory model and animal studies.  Future applications of the system in precision medicine will explore the use of the device for selecting patient-specific therapies for cancer.
  • 704
  • 26 Oct 2020
Topic Review
Targeting Liver Cancer Stem Cells
       Cancer stem cells (CSCs) are known to be highly resistant to conventional therapeutic approaches, such as chemotherapeutic drugs and radiation. Therefore, selectively targeting CSCs with specific markers or signaling pathways can be an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. However, there is not enough information currently available to make a conclusive statement regarding hepatic CSC-specific signaling pathways and biomarkers. In present study, we provide an overview of the current knowledge on the specific surface markers and critical signaling pathways of hepatic CSC.
  • 704
  • 29 Oct 2020
Topic Review
Genomics-Driven Precision Medicine in Pediatric Solid Tumors
The detection of genomic aberrations in cancers has yielded a wealth of information to discover oncogenic drivers or pathogenic variants that are relevant for the development of precise treatment strategies. Studies have shown promising outcomes in adult cancer patients with well characterized cancer genetic biomarkers.
  • 704
  • 17 Mar 2023
Topic Review
Immune Microenvironment of Malignant Gliomas
Single-cell technologies allow precise identification of tumor composition at the single-cell level, providing high-resolution insights into the intratumoral heterogeneity and transcriptional activity of cells in the tumor microenvironment (TME) that previous approaches failed to capture. Malignant gliomas, the most common primary brain tumors in adults, are genetically heterogeneous and their TME consists of various stromal and immune cells playing an important role in tumor progression and responses to therapies. Previous gene expression or immunocytochemical studies of immune cells infiltrating TME of malignant gliomas failed to dissect their functional phenotypes. Single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) are powerful techniques allowing quantification of whole transcriptomes or >30 protein targets in individual cells. Both methods provide unprecedented resolution of TME. 
  • 702
  • 17 Sep 2021
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