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Topic Review
ALDH in Gynecologic Malignancies
Gynecologic cancers cause over 600,000 deaths annually in women worldwide. The development of chemoresistance after initial rounds of chemotherapy contributes to tumor relapse and death due to gynecologic malignancies. In this regard, cancer stem cells (CSCs), a subpopulation of stem cells with the ability to undergo self-renewal and clonal evolution, play a key role in tumor progression and drug resistance. Aldehyde dehydrogenases (ALDH) are a group of enzymes shown to be robust CSC markers in gynecologic and other malignancies. These enzymes also play functional roles in CSCs, including detoxification of aldehydes, scavenging of reactive oxygen species (ROS), and retinoic acid (RA) signaling, making ALDH an attractive therapeutic target in various clinical scenarios. In this review, we discuss the critical roles of the ALDH in driving stemness in different gynecologic malignancies. We review inhibitors of ALDH, both general and isoform-specific, which have been used to target CSCs in gynecologic cancers. Many of these inhibitors have been shown to be effective in preclinical models of gynecologic malignancies, supporting further development in the clinic. Furthermore, ALDH inhibitors, including 673A and CM037, synergize with chemotherapy to reduce tumor growth. Thus, ALDH-targeted therapies hold promise for improving patient outcomes in gynecologic malignancies.
  • 1.1K
  • 20 Feb 2021
Topic Review
Delivery vehicles in Veterinary Oncology
Nanomedicine is a recent concept in veterinary oncology and provide the possibility of more specific treatment to the patients. In this critical review, we provided the most updated information regarding the use of nanoparticles in veterinary oncology. 
  • 1.1K
  • 26 Oct 2020
Topic Review
Cyclin-Dependent Kinases Pathway Dysregulation in Soft Tissue Sarcoma
Soft tissue sarcomas (STSs) are rare malignant conditions with more than 70 subtypes that are difficult to treat, especially in advanced or metastatic states. Next-generation sequencing technologies have provided comprehensive information and developed personalized medicine for treating cancer in general and STSs in particular. Growing knowledge of diverse gene alterations and biomolecular targets in various subtypes of STSs raises hope for novel treatment approaches and heralds a paradigm shift in the treatment of STSs. Activated cyclin-dependent kinases (CDKs) appear to play a critical role in sarcoma development and represent important targets for sarcoma therapy. 
  • 1.1K
  • 18 Aug 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
Berberine - Supportive Action Cancer
Berberine is very promising as the anticancer agent. Berberine not only possesses documented proapoptotic activity, which is in the focus of attention, but also seems to be a very important and promising compound in combined cancer treatment. Sensitization and elimination of drug resistance are very promising trends in the berberine research. What is more, berberine exhibits low toxicity towards healthy cells, which makes it safe for clinical use and proves its activity in biochemical disorders. 
  • 1.1K
  • 23 Nov 2020
Topic Review
Genetic Aspects of Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are myeloid neoplasms characterized by the presentation of overlapping features from both myelodysplastic syndromes and myeloproliferative neoplasms. Although the classification of MDS/MPN relies largely on clinical features and peripheral blood and bone marrow morphology, studies have demonstrated that a large proportion of patients (~90%) with this disease harbor somatic mutations in a group of genes that are common across myeloid neoplasms. These mutations play a role in the clinical heterogeneity of these diseases and their clinical evolution. 
  • 1.1K
  • 31 May 2021
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
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.
  • 1.1K
  • 02 Nov 2022
Topic Review
Targeted Therapies in Advanced BTCs
Biliary tract cancers (BTCs) are a heterogeneous group of adenocarcinomas characterized by presentation with advanced disease and a poor prognosis. Chemotherapy is the mainstay of the current treatment that provides limited survival benefit, underscoring the need for novel therapeutic agents and strategies. Next-generation sequencing-based molecular profiling has shed light on the underpinnings of the complex pathophysiology of BTC and has uncovered numerous actionable targets, leading to the discovery of new therapies tailored to the molecular targets. Therapies targeting fibroblast growth factor receptor (FGFR) fusion, isocitrate dehydrogenase (IDH) mutations, the human epidermal growth factor receptor (HER) family, DNA damage repair (DDR) pathways, and BRAF mutations have produced early encouraging results in selected patients. Current clinical trials evaluating targeted therapies, as monotherapies and in combination with other agents, are paving the way for novel treatment options. Genomic profiling of cell-free circulating tumor DNA that can assist in the identification of an actionable target is another exciting area of development. The present article provides an overview of a precision medicine centered evolving paradigm of BTC treatment.
  • 1.1K
  • 12 Aug 2020
Topic Review
Radiotherapy Considerations for Nasopharyngeal Carcinoma
Radiotherapy is the primary treatment modality for nasopharyngeal carcinoma (NPC). Successful curative treatment requires optimal radiotherapy planning and precise beam delivery that maximizes locoregional control while minimizing treatment-related side effects.
  • 1.1K
  • 06 Feb 2023
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.
  • 1.1K
  • 20 Jan 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.
  • 1.1K
  • 03 Nov 2020
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
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
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
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.
  • 1.1K
  • 29 Feb 2024
Topic Review
Golgi Dynamics in Cancer Metastasis
The Golgi apparatus is at the center of protein processing and trafficking in normal cells. Under pathological conditions, such as in cancer, aberrant Golgi dynamics alter the tumor microenvironment and the immune landscape, which enhances the invasive and metastatic potential of cancer cells. Among these changes in the Golgi in cancer include altered Golgi orientation and morphology that contribute to atypical Golgi function in protein trafficking, post-translational modification, and exocytosis. Golgi-associated gene mutations are ubiquitous across most cancers and are responsible for modifying Golgi function to become pro-metastatic. The pharmacological targeting of the Golgi or its associated genes has been difficult in the clinic; thus, studying the Golgi and its role in cancer is critical to developing novel therapeutic agents that limit cancer progression and metastasis.
  • 1.1K
  • 31 May 2022
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.
  • 1.1K
  • 01 Jul 2022
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
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
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