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Topic Review
Neurokinin-1 Receptor Antagonists as Therapeutic Agent for Osteosarcoma
Osteosarcoma is a bone tumor predominantly affecting children and adolescents with high malignant potential. It is a cause of serious public health challenges due to its high morbidity rates and metastatic potential. Metastasis in osteosarcoma may manifest either during treatment of the primary tumor, shortly after treatment, or a long time after the end of the treatment. So far, there are no therapeutics that can prevent or treat osteosarcoma metastasis. The peptide substance P (SP) and its high-affinity receptor, Neurokinin-1 (NK-1R), are known to positively correlate with osteosarcoma progression. Osteosarcoma cells overexpress NK-1R. SP is known to elicit the proliferation of osteosarcoma cells and induce angiogenesis and migration, leading to the invasion and metastasis of tumor cells. In contrast, NK-1R antagonists, such as aprepitant, inhibit the proliferation and induce the apoptosis of osteosarcoma cells. Aprepitant is also known to inhibit the migration of osteosarcoma cells, as well as reduce the expression levels and activities of transcriptional regulators of metastasis-related genes such as matrix metalloproteinases (MMP-2 and MMP-9), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-κB). These preceding studies highlighted the antimetastatic role of aprepitant in osteosarcoma Moreover, combination therapy consisting of chemotherapy and NK-1R antagonist increases the chemosensitization of osteosarcoma cells.
  • 623
  • 28 Mar 2023
Topic Review
Bone Metastases from Gastric Cancer
Gastric cancer (GC) is the third cause of cancer-related death worldwide; the prognosis is poor especially in the case of metastatic disease; bone metastases are rare. Their impact on prognosis is still under debate.
  • 622
  • 10 May 2021
Topic Review
PD-L1 Expression
Immune checkpoint inhibitors (ICIs) such as PD1/PD-L1 blockers are an established treatment for many solid cancers. There are currently no approved ICIs for sarcomas, but satisfactory results have been seen in some patients with disseminated disease in certain histological types. Most studies on PD-L1 in sarcoma have used small specimens and there are no clear cutoff values for scoring.
  • 622
  • 28 Feb 2022
Topic Review
Precision Anti-Cancer Medicines by Oligonucleotide in Clinical Reasearch
Oligonucleotide therapeutics enable a direct targeting of the gene by acting at the level of the RNA or at the level of the DNA, based on the Watson-Crick complementary rule of binding.
  • 622
  • 29 Jul 2022
Topic Review
Immune Checkpoint Blockade in Acute Myeloid Leukemia
Acute myeloid leukemia is an aggressive and very lethal blood tumor. It represents a substantial percentage of leukemia patients, as well as leukemic deaths. Immune checkpoint inhibition (ICI) has emerged as a therapeutic option for acute myeloid leukemia (AML) for patients that suffer from relapsed or high-risk disease, or patients ineligible for standard therapy.
  • 622
  • 04 Aug 2022
Topic Review
Biomarkers for Breast Cancer
Breast cancer is the most commonly diagnosed cancer type and the leading cause of cancer-related mortality in women worldwide. Breast cancer is fairly heterogeneous and reveals six molecular subtypes: luminal A, luminal B, HER2+, basal-like subtype (ER−, PR−, and HER2−), normal breast-like, and claudin-low. Breast cancer screening and early diagnosis play critical roles in improving therapeutic outcomes and prognosis. Mammography is currently the main commercially available detection method for breast cancer; however, it has numerous limitations. Therefore, reliable noninvasive diagnostic and prognostic biomarkers are required. Biomarkers used in cancer range from macromolecules, such as DNA, RNA, and proteins, to whole cells. Biomarkers for cancer risk, diagnosis, proliferation, metastasis, drug resistance, and prognosis have been identified in breast cancer. In addition, there is currently a greater demand for personalized or precise treatments; moreover, the identification of novel biomarkers to further the development of new drugs is urgently needed.
  • 621
  • 23 Feb 2021
Topic Review
HLA-I and Cancer Derived Extracellular Vesicles
The Human Leukocyte Antigen class I (HLA-I) system is an essential part of the immune system that is fundamental to the successful activation of cytotoxic lymphocytes, and an effective subsequent immune attack against both pathogen-infected and cancer cells. The importance of cytotoxic T cell activity and ability to detect foreign cancer-related antigenic peptides has recently been highlighted by the successful application of monoclonal antibody-based checkpoint inhibitors as novel immune therapies. Thus, there is an increased interest in fully characterising the repertoire of peptides that are being presented to cytotoxic CD8+ T cells by cancer cells. However, HLA-I is also known to be present on the surface of extracellular vesicles, which are released by most if not all cancer cells. Whilst the peptide ligandome presented by cell surface HLA class I molecules on cancer cells has been studied extensively, the ligandome of extracellular vesicles remains relatively poorly defined.
  • 621
  • 13 Jan 2022
Topic Review
Cutaneous Immune-Related Adverse Events
Dermatologic complications arise as the earliest and most frequently observed adverse events among all immune-related adverse events (irAEs), affecting between 30 and 50% of patients on Immune checkpoint inhibitors (ICIs). The symptoms may significantly impair patients’ quality of life, and even lead to a pause of immunotherapy treatment. Fortunately, the majority of cirAEs seem to be mild and manageable, but there are still a few serious events (grade III or IV) being observed. Maculopapular rash, pruritus, lichenoid eruptions, and vitiligo are the most widely reported cutaneous adverse events. Severe cutaneous adverse reactions (SCARs), consisting of Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug rash with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), are rare but potentially life-threatening. Other less-frequent manifestations include ICI-induced dermatomyositis, Sweet syndrome, interstitial granulomatous dermatitis, pityriasis rubra pilaris-like erythroderma, and lupus-like cutaneous reaction.
  • 621
  • 28 Apr 2022
Topic Review
MicroRNAs in EMT of Cancer
In the last decades, a kind of small non-coding RNA molecules, called as microRNAs, has been applied as negative regulators in various types of cancer treatment through down-regulation of their targets. More recent studies exert that microRNAs play a critical role in the EMT process of cancer, promoting or inhibiting EMT progression. Interestingly, accumulating evidence suggests that pure compounds from natural plants could modulate deregulated microRNAs to inhibit EMT, resulting in the inhibition of cancer development. This small essay is on the purpose of demonstrating the significance and function of microRNAs in the EMT process as oncogenes and tumor suppressor genes according to studies mainly conducted in the last four years, providing evidence of efficient target therapy.
  • 621
  • 23 Jul 2021
Topic Review
Active Targeted Nanoparticles
PARP inhibitors were introduced as tools to protect from inflammatory diseases. Later, these selective inhibitors were evaluated as nanotherapeutic agents in clinical trials as targeted treatment strategies against solid tumors derived from ovarian, prostate, breast, colorectal, and uterine tissues. Although previous reports have established that PARP inhibitors effectively treat BRCA1-deficient cancers and increase patients’ progression-free survival (PFS), new studies have suggested that HR-deficient cells may also be vulnerable to PARP inhibition.
  • 620
  • 10 Nov 2021
Topic Review
LOXL2 Inhibitors and Breast Cancer Progression
LOX (lysyl oxidase) and lysyl oxidase like-1–4 (LOXL 1–4) are amine oxidases, which catalyze cross-linking reactions of elastin and collagen in the connective tissue. These amine oxidases also allow the cross-link of collagen and elastin in the extracellular matrix of tumors, facilitating the process of cell migration and the formation of metastases. LOXL2 is of particular interest in cancer biology as it is highly expressed in some tumors. This protein also promotes oncogenic transformation and affects the proliferation of breast cancer cells. LOX and LOXL2 inhibition have thus been suggested as a promising strategy to prevent metastasis and invasion of breast cancer. BAPN (β-aminopropionitrile) was the first compound described as a LOX inhibitor and was obtained from a natural source.
  • 620
  • 23 May 2022
Topic Review
CN133
Pediatric ependymoma (EPN) is a highly aggressive tumor of the central nervous system that remains incurable in 40% of cases. In children, the majority of cases develop in the posterior fossa and can be classified into two distinct molecular entities: EPN posterior fossa A (PF-EPN-A) and EPN posterior fossa B (PF-EPN-B). Patients with PF-EPN-A have poor outcome and are in demand of new therapies. In general, PF-EPN-A tumors show a balanced chromosome copy number profile and have no recurrent somatic nucleotide variants. However, these tumors present abundant epigenetic deregulations, thereby suggesting that epigenetic therapies could provide new opportunities for PF-EPN-A patients. In vitro epigenetic drug screening of 11 compounds showed that histone deacetylase inhibitors (HDACi) had the highest anti-proliferative activity in two PF-EPN-A patient-derived cell lines. Further screening of 5 new brain-penetrating HDACi showed that CN133 induced apoptosis in vitro, reduced tumor growth in vivo and significantly extended the survival of mice with orthotopically-implanted EPN tumors by modulation of the unfolded protein response, PI3K/Akt/mTOR signaling, and apoptotic pathways among others.
  • 620
  • 09 Apr 2021
Topic Review
Muscle-Invasive Urothelial Carcinoma in Dogs
Muscle-invasive urothelial carcinoma (MIUC) is the most common type of bladder malignancy in humans, but also in dogs that represent a naturally occurring model for this disease. Dogs are immunocompetent animals that share risk factors, pathophysiological features, clinical signs and response to chemotherapeutics with human cancer patients. 
  • 620
  • 27 Oct 2021
Topic Review
Local Treatment Options for BCC
Cutaneous basal cell carcinoma (BCC) is the most common human tumour and its incidence is rising worldide. Until a few years ago, the therapeutic options were limited fo patients with advanced BCC including both metastatic and locally-advanced BCC. Over the last years, promising systemic therapies have been investigated for the treatments of advanced BCC. In particular, the Hedgehog signaling inhibition have shown remarkable results for this population. Currently, the Hedgehog inhibitors representing by vismodegib and sonidegib are approved be the Food and Drug Administration and European Medicines Agency for the treatment of both locally advanced and metastatic BCC with generally a well safety profile. 
  • 619
  • 07 Dec 2020
Topic Review
Hilar Biliary Obstruction
Malignant hilar biliary obstruction (HBO) represents a complex clinical condition in terms of diagnosis, surgical and medical treatment, endoscopic approach, and palliation. The main etiology of malignant HBO is hilar cholangiocarcinoma that is considered an aggressive biliary tract’s cancer and has still today a poor prognosis.
  • 619
  • 18 Mar 2021
Topic Review
Metabolomics-Microbiome Crosstalk in Breast Cancer Microenvironment
The human microbiome is defined as the full array of the diverse microorganisms (microbiota) that live on and in humans, as well as their genetic materials. It is considered one of the leading environmental factors in disease development, with Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria dominant species. Human microbiota manifestation is influenced by multiple environmental and physiological changes, including age, sex, race, geography, diet, host genetics and lifestyle, drugs like antibiotics, and interaction with the immune system and metabolic pathway.
  • 619
  • 11 Nov 2021
Topic Review
The Eclectic Nature of Glioma-Infiltrating Macrophages and Microglia
Glioblastomas (GBMs) are complex ecosystems composed of highly multifaceted tumor and myeloid cells capable of responding to different environmental pressures, including therapies. Recent studies have uncovered the diverse phenotypical identities of brain-populating myeloid cells. Differences in the immune proportions and phenotypes within tumors seem to be dictated by molecular features of glioma cells. Furthermore, increasing evidence underscores the significance of interactions between myeloid cells and glioma cells that allow them to evolve in a synergistic fashion to sustain tumor growth.
  • 619
  • 21 Jan 2022
Topic Review
Reactive Oxygen Species in Acute Lymphoblastic Leukaemia
Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children and adolescents. Approximately 70% of patients survive >5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers and are emerging as significant contributors to the leukaemogenesis of ALL. ROS modulate the function of signalling proteins through oxidation of cysteine residues, as well as promote genomic instability by damaging DNA, to promote chemotherapy resistance. Current therapeutic approaches exploit the pro-oxidant intracellular environment of malignant B and T lymphoblasts to cause irreversible DNA damage and cell death, however these strategies impact normal haematopoiesis and lead to long lasting side-effects. Therapies suppressing ROS production, especially those targeting ROS producing enzymes such as the NADPH oxidases (NOXs), are emerging alternatives to treat cancers and may be exploited to improve the ALL treatment. 
  • 619
  • 02 Apr 2022
Topic Review
Adenocarcinoma of the Colon
Adenocarcinoma of the colon is the most common malignant neoplasia of the gastrointestinal tract and is a major contributor to mortality worldwide. Invasiveness and metastatic behavior are typical of malignant tumors and, because of its portal drainage, the liver is the closest capillary bed available in this case, hence the common site of metastatic dissemination. Current therapies forecast total resection of primary tumor when possible and partial liver resection at advanced stages, along with systemic intravenous therapies consisting of chemotherapeutic agents such as 5-fluorouracil. These cures are definitely not exempt from drawbacks and heavy side effects. Biocompatible polymeric networks, both in colloids and bulk forms, able to absorb large quantities of water and load a variety of molecules-belong to the class of innovative drug delivery systems, thus suitable for the purpose and tunable on each patient can represent a promising alternative. Indeed, the implantation of polymeric scaffolds easy to synthesize can substitute chemotherapy and combination therapies scheduling, shortening side effects. Moreover, they do not require a surgical removal thanks to spontaneous degradation and guarantees an extended and regional cargo release, maintaining high drug concentrations.
  • 618
  • 22 Jan 2021
Topic Review
LncRNAE2F4
LncRNA is a promising biomarker that predicts the prognosis of a variety of cancers, but the important role of E2F4antisense lncRNA in cancer remains unclear.  E2F4as was highly expressed in ovarian cancer patients, and that the higher the expression of E2F4as, the worse the patient’s prognosis. 
  • 617
  • 18 Dec 2020
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