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Topic Review
3D Modeling of Epithelial Tumors
The current statistics on cancer show that 90% of all human cancers originate from epithelial cells. Breast and prostate cancer are examples of common tumors of epithelial origin that would benefit from improved drug treatment strategies. About 90% of preclinically approved drugs fail in clinical trials, partially due to the use of too simplified in vitro models and a lack of mimicking the tumor microenvironment in drug efficacy testing. This entry focuses on the epithelial cancers, followed by experimental models designed to recapitulate the epithelial tumor structure and microenvironment. A specific focus is to put on novel technologies for cell culture of spheroids, organoids, and 3D-printed tissue-like models, utilizing biomaterials of natural or synthetic origins, and how the models could be utilized for nanotechnology-based drug delivery in the future.
  • 759
  • 24 Jun 2021
Topic Review
Oligometastatic Breast Cancer
Breast cancer (BC) is the most frequent cancer among women and represents the second leading cause of cancer-specific death. A subset of patients with metastatic breast cancer (MBC) presents limited disease, termed ‘oligometastatic’ breast cancer (OMBC). The oligometastatic disease can be managed with different treatment strategies to achieve long-term remission and eventually cure. Several approaches are possible to cure the oligometastatic disease: locoregional treatments of the primary tumor and of all the metastatic sites, such as surgery and radiotherapy; systemic treatment, including target-therapy or immunotherapy, according to the biological status of the primary tumor and/or of the metastases; or the combination of these approaches. Encouraging results involve local ablative options, but these trials are limited by being retrospective and affected by selection bias. Systemic therapy, e.g., the use of CDK4/6 inhibitors for hormone receptor-positive (HR+)/HER-2 negative BC, leads to an increase of progression-free survival (PFS) and overall survival (OS) in all the subgroups, with favorable toxicity. Regardless of the lack of substantial data, this subset of patients could be treated with curative intent; the appropriate candidates could be mostly young women, for whom a multidisciplinary aggressive approach appears suitable.
  • 759
  • 25 Jun 2021
Topic Review
Lynch Syndrome (LS)
Lynch syndrome (LS), also known as Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is an autosomal dominant cancer syndrome which causes about 2–3% of cases of colorectal carcinoma. The development of LS is due to the genetic and epigenetic inactivation of genes involved in the DNA mismatch repair (MMR) system, causing an epiphenomenon known as microsatellite instability (MSI). 
  • 759
  • 22 Aug 2023
Topic Review
Immunomodulation in Pancreatic Cancer
The majority of pancreatic cancer patients have a poor prognosis, where the five-year survival rate is 9% in the United States, with an increasing incidence rate of 1.03% per year. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of pancreatic cancer that makes up 90% of all diagnosed cases of pancreatic cancer. Other types of pancreatic cancer, such as neuroendocrine tumors, which secrete insulin, or acinar carcinomas, which release digestive enzymes, are less common. PDAC develops from neoplasms of the cells lining the pancreatic ducts and usually presents without symptoms until advanced stages of the disease. Here we discuss strategies for immunomodulation of pancreatic cancer.
  • 758
  • 26 Nov 2020
Topic Review
Peptide Drug Conjugates in Cancer Therapy
Drug conjugates have become a significant focus of research in the field of targeted medicine for cancer treatments. Peptide-drug conjugates (PDCs), a subset of drug conjugates, are composed of carrier peptides ranging from 5 to 30 amino acid residues, toxic payloads, and linkers that connect the payload to the peptide. PDCs are further broken down into cell-penetrating peptides (CPPs) and cell-targeting peptides (CTPs), each having their own differences in the delivery of cytotoxic payloads. Generally, PDCs as compared to other drug conjugates—like antibody-drug conjugates (ADCs)—have advantages in tumor penetration, ease of synthesis and cost, and reduced off-target effects. Further, as compared to traditional cancer treatments (e.g., chemotherapy and radiation), PDCs have higher specificity for the target cancer with generally less toxic side effects in smaller doses. 
  • 758
  • 19 Jan 2023
Topic Review
Gamma-Interferon in Cancer Hyperprogression
Immune checkpoint inhibitors (ICIs) improve the survival of patients with multiple types of cancer. However, low response rates and atypical responses limit their success in clinical applications. The paradoxical acceleration of tumor growth after treatment, defined as hyperprogressive disease (HPD), is the most difficult problem facing clinicians and patients alike. The mechanisms that underlie hyperprogression (HP) are still unclear and controversial, although a large number of studies have investigated the phenomenon and several associated factors have been reported. Gamma-interferon (IFN-γ) is a key cytokine in antitumor response and its levels increase during ICI therapy. Even though this factor has been widely associated with resistance to ICI therapy, it has not yet been demonstrated to be directly associated with HP. Nevertheless, data suggest that IFN-γ may contribute to HP onset through different mechanisms, including the activation of the inflammasome pathway, the expression of the immunosuppressive enzyme IDO1 and the triggering of activation-induced cell death (AICD) in effector T cells. These findings make IFN-γ worthy of attention in the context of HPD development.
  • 757
  • 07 Feb 2021
Topic Review
Cancer Vaccines
Therapeutic cancer vaccines target TAAs alongside adjuvant molecules that can elicit specific antibodies or cytotoxic immune responses against cancer cells. There are different ways to present TAAs to the immune system. DNA and RNA encoding TAAs or whole peptides can be recognized and processed by the APCs; tumor cell lines express TAAs and can chemotactically attract APCs; viral vectors transfect APCs after being loaded with prespecified antigens; finally, DCs act as APCs and can be loaded with TAAs.
  • 756
  • 29 Mar 2022
Topic Review
Anti-Cancer Effects of Oleuropein
Longevity and lower morbidity and mortality have long been associated with olive oil use in the Mediterranean diet. Olive leaves have been used to treat malaria fever since ancient times, and numerous studies have shown that olive oil and olive leaves can enhance health by reducing cardiovascular and neurological illnesses. Oleuropein (Ole) is the principal phenolic chemical found in all sections of the olive tree Olea europaea L., and their health advantages are described below, as it is found in all parts of the tree, particularly in raw olive fruit and leaves. Ole is an ester of oleanolic acid and hydroxytyrosol (HT), which was discovered in 1908. Ole aglycone is generated when Ole is hydrolyzed during the mechanical extraction of green olives, and it has a bitter taste. Ole is broken down into HT, which is found in abundance in processed olive oil and fruit. Ole can be degraded chemically or enzymatically. Many factors influence the amount of Ole in olive trees, including cultivar and production area, as well as soil moisture content, pollutants, and atmospheric conditions.
  • 756
  • 12 Aug 2022
Topic Review
Tumour Immune Microenvironment
Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. In this entry, we focus on the metabolic dysregulation exerted by tumour cells on the immune microenvironment, leading to tumour immunosuppression. This metabolic rewiring and crosstalk with the tumour microenvironment also play a key role in cell proliferation, metastasis, and the development of treatment resistance. Nonetheless, greater understanding of the metabolic crosstalk presents strategies that aid in the precision targeting of altered tumour metabolism, including therapeutic strategies combining metabolic inhibition with immunotherapy.
  • 756
  • 09 Dec 2020
Topic Review
Biliary Tract Cancers
Biliary tract carcinomas (BTCs) are a heterogeneous group of malignancies arising from the epithelial lining of the bile ducts or gallbladder.
  • 756
  • 28 Oct 2021
Topic Review
Wnt Pathway: A Tailored Target
Cancer represents one of the greatest public health challenges. One of the most cancer-driving events embodies the dysregulation of both the canonical and the non-canonical Wnt/β-catenin pathway. The impact of the Wnt/β-catenin pathway has been widely reviewed in colorectal, breast, and ovarian cancers.  Genetic and epigenetic alterations are commonly detected in colorectal cancers (CRCs). As a matter of fact, 70% of CRCs are connoted by the APC mutations and almost all patients display an overactive Wnt/β-catenin pathway also mediated by oncogenic miRNAs. Therefore, miRNAs have been proposed as anti-cancer and/or diagnostic/prognostic tools. Among cancers, breast cancer (BC) is one of the most expensive health care costs with a high rate of diagnosis and deaths per year. The Wnt/β-catenin cascade and in particular the β-catenin content has been correlated with a dismal prognosis, high tumour grade, and metastasis formation. In addition in triple-negative breast cancer (TNBC) both the canonical and the non-canonical Wnt/β-catenin pathways have been reported as drivers of cancer dissemination, aggressiveness, early age of onset, and poor outcome. To add further complexity, the Wnt5a ligand was found to display both anti-tumour and tumour promoting properties depending on the tumour microenvironment (TME), the activation of specific signalling pathways, and the receptor availability in BC.  Likewise, an abnormal Wnt/β-catenin cascade has been shown to strongly contribute to ovarian cancer (OC) growth, stemness, and drug resistance.  In the last decades, particular attention has been dedicated to investigate the role of extracellular vesicles (EVs) released in the TME in cancer growth and progression. EVs are heterogeneous small membrane-bound carriers with a complex cargo contributing to cell-to-cell communication, tumour growth, invasion, and chemoresistance. Since EVs can be detected in the majority of biological fluids and in the TME, EVs have been proposed as diagnostic and/or prognostic tools, as well as useful therapeutic options. Indeed, EVs engineered with specific anti-tumour molecules or loaded with conventional anti-tumour drugs have been proposed as novel anti-cancer options. Based on these notions, in the last decades, Wnt/β catenin targeting approaches have been explored to hinder tumour expansion. However so far, the most relevant limitation relies on the crucial role played by the Wnt/β catenin cascade in tissue homeostasis. Therefore, to develop targeting approaches the identification of the specific EV cargo driving tumour progression and the mechanisms accounting for the unbalanced Wnt/β catenin pathway in cancer should be considered as the most challenging issues.
  • 755
  • 03 Nov 2020
Topic Review
Neurodevelopmental Consequences of Pediatric Cancer
Cognitive impairment is frequent in pediatric cancer, and behavioral and psychological disturbances often also affect children who have survived cancer problems. Furthermore, pediatric tumors are also often associated with sleep disorders. 
  • 755
  • 23 Jun 2021
Topic Review
Measurable Residual Disease in AML
Relapse is still a major problem in AML because it occurs in about 60–80% of patients, even those who have previously achieved complete remission (CR), defined by the presence of ≤5% bone marrow (BM) leukemic cells. Thus, since CR is unable to predict the relapse risk, significantly more sensitive techniques aimed at identifying AML cells in BM or peripheral blood, a parameter termed measurable residual disease (MRD), have been developed. Among them, RT-qPCR, which analyses appropriate molecular markers, and multiparameter flow cytometry (MFC), which analyses aberrantly expressed antigens, have been identified as the methods of choice for MRD detection. 
  • 755
  • 22 Sep 2021
Topic Review
Nuclear Matrix Metalloproteinases
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to facilitate cellular growth, migration, and metastasis of tumor cells during cancer progression. A growing number of these proteins are being found to exist in the nuclei of both healthy and tumor cells, thus highlighting their localization as having a genuine purpose in cellular homeostasis. The mechanism underlying nuclear transport and the effects of MMP nuclear translocation have not yet been fully elucidated. To date, nuclear MMPs appear to have a unique impact on cellular apoptosis and gene regulation, which can have effects on immune response and tumor progression, and thus present themselves as potential therapeutic targets in certain types of cancer or disease. Herein, we highlight and evaluate what progress has been made in this area of research, which clearly has some value as a specific and unique way of targeting the activity of nuclear matrix metalloproteinases within various cell types. 
  • 754
  • 05 Jan 2021
Topic Review
Pancreatic Ductal Adenocarcinoma Therapy
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in the US, and it is expected to be the second leading cause of cancer deaths by 2030. The lack of effective early screening tests and alarming symptoms with early undetectable micro-metastasis at the time of presentation play a vital role in the high death rate from pancreatic cancer. In addition to this, the low mutation burden in pancreatic cancer, low immunological profile, dense tumorigenesis stroma, and decreased tumor sensitivity to cytotoxic drugs contribute to the low survival rates in PDAC patients. Despite breakthroughs in chemotherapeutic and immunotherapeutic drugs, pancreatic cancer remains one of the solid tumors that exhibit meager curative rates.
  • 754
  • 23 Jun 2021
Topic Review
Pterostilbene in Cancer Therapy
Natural polyphenols are organic chemicals which contain phenol units in their structures and possess antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Pterostilbene (3,5-dimethoxy-4'-hydroxystilbene; PT) is a phytoalexin originally isolated from the heartwood of red sandalwood. As recently reported by our group, PT was shown to be effective in the treatment of melanoma. Counterintuitively, PT is not effective (cytotoxic) against melanoma in vitro, and only under in vivo conditions does PT display its anticancer activity. This study elucidated that PT can be effective against melanoma through the inhibition of adrenocorticotropic hormone production in the brain of a mouse, which weakens the Nrf2-dependent antioxidant defenses of melanoma and also pancreatic cancers. This results in both the inhibition of tumor growth and sensitization of the tumor to oxidative stress. Moreover, PT can promote cancer cell death via a mechanism involving lysosomal membrane permeabilization. Different grades of susceptibility were observed among the different cancer cells depending on their lysosomal heat shock protein 70 content, a known stabilizer of lysosomal membranes. In addition, the safety of PT administered i.v. has been evaluated in mice. PT was found to be pharmacologically safe because it showed no organ-specific or systemic toxicity (including tissue histopathologic examination and regular hematology and clinical chemistry data) even when administered i.v. at a high dose (30 mg/kg per day × 23 days). Moreover, new pharmacological advances are being developed to increase its bioavailability and, thereby, its bioefficacy. Therefore, although applications of PT in cancer therapy are just beginning to be explored, it represents a potential (and effective) adjuvant/sensitizing therapy which may improve the results of various oncotherapies. The aim of this review is to present and discuss the results that in our opinion best support the usefulness of PT in cancer therapy, making special emphasis on the in vivo evidence.
  • 753
  • 26 Jul 2021
Topic Review
L-Ascorbic Acid for Non-Melanoma Cancer
L-ascorbic acid, is a well-known molecule, sometimes used as antioxidant for skin care. Nonetheless, few studies have taken in account its utility as topical treatment for non-melanoma skin cancer. Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma and is widespread worldwide with an increasing incidence.
  • 753
  • 29 Mar 2022
Topic Review
Syngeneic Mouse Models for Therapeutic Research in OC
The most prevalent oral cancer globally is oral squamous cell carcinoma (OSCC). The invasion of adjacent bones and the metastasis to regional lymph nodes often lead to poor prognoses and shortened survival times in patients with OSCC. Encouraging immunotherapeutic responses have been seen with immune checkpoint inhibitors (ICIs); however, these positive responses to monotherapy have been limited to a small subset of patients. Therefore, it is urgent that further investigations into optimizing immunotherapies are conducted. Areas of research include identifying novel immune checkpoints and targets and tailoring treatment programs to meet the needs of individual patients. Furthermore, the advancement of combination therapies against OSCC is also critical. Thus, additional studies are needed to ensure clinical trials are successful. Mice models are advantageous in immunotherapy research with several advantages, such as relatively low costs and high tumor growth success rate. 
  • 753
  • 01 Sep 2022
Topic Review
Biomarkers in Prostate Cancer Diagnosis
Early detection of prostate cancer (PC) is largely carried out using assessment of prostate-specific antigen (PSA) level; yet it cannot reliably discriminate between benign pathologies and clinically significant forms of PC. Exosomes are extracellular vesicles that are secreted from all mammalian cells and virtually detected in all bio-fluids, thus allowing their use as tumor biomarkers.
  • 752
  • 04 Jun 2021
Topic Review
Trophoblast Cell Surface Antigen-2 in Cancer
Trophoblast cell surface antigen-2 (Trop-2) is a glycoprotein that was first described as a membrane marker of trophoblast cells and was associated with regenerative abilities. Trop-2 overexpression was also described in several tumour types. Nevertheless, the therapeutic potential of Trop-2 was widely recognized and clinical studies with drug–antibody conjugates have been initiated in various cancer types. 
  • 752
  • 31 Mar 2023
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