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Gastric cancer represents one of the most frequent and lethal tumors worldwide today, finding itself in the fifth place in incidence and the third in mortality. Surgery remains the only curative treatment for localized tumors, but only 20% of patients are suitable for surgery due to the lack of specific symptoms and the late diagnosis, especially in Western countries. Additionally, even in patients who receive curative treatment, rates of locoregional relapse and distant metastasis remain high. Palliative chemotherapy is the principal treatment in cases of metastatic disease even if the prognosis of patients receiving chemotherapy is still poor. Therefore, a multidisciplinary evaluation is important in order to improve the efficacy of active treatments. In this context, there is an unmet need for a better understanding of genetic alterations and prognostic and predictive factors in order to choose the best tailored therapy for each patient. The aim of this Special Issue is to focus on the results and problems of multimodality treatment in metastatic gastric cancer, the search for prognostic and predictive factors, and the evaluation of novel strategies for individualized treatment. We are inviting relevant original research, systematic reviews, meta-analyses, and short communications covering the above-mentioned topics.

advanced gastric cancer --- precision medicine --- new drug development --- gastro-oesophageal cancer --- mutational concordance --- exome sequencing --- formalin fixed paraffin embedded --- biomarkers --- gastric cancer --- metastatic --- body composition --- sarcopenia --- visceral fat area --- subcutaneous fat area --- outcome --- toxicity --- liver metastasis --- conversion surgery --- hepatectomy --- stage iv gastric cancer --- immune checkpoint inhibitors --- Epstein Barr Virus --- tumor mutational burden --- microsatellite instability --- predictive biomarkers --- CAR T cell therapy --- vaccines --- nutritional status --- metastatic gastric cancer --- target therapy --- bone flare --- stage IV --- treatment --- RANK-L --- liquid biopsy --- circulating tumor cell --- cfDNA --- ctDNA --- epithelial–mesenchymal transition --- resistance to treatment --- HER2-inhibition --- VEGFR-inhibition --- immunotherapy --- response monitoring --- n/a --- epithelial-mesenchymal transition

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Despite the efficiency of current cancer treatments, cancer is still a deadly disease for too many. In 2008, 7.6 million people died of cancer; with the current development, it is estimated that the annual cancer death number will grow to 13 million by 2030. There is clearly a need for not only more research but also more innovative and out of the mainstream scientific ideas to discover and develop even better cancer treatments. This book presents the collective works published in the recent Special Issue entitled “Killing Cancer: Discovery and Selection of New Target Molecules”. These articles comprise a selection of studies, ideas, and opinions that aim to facilitate knowledge, thoughts, and discussion about which biological and molecular mechanisms in cancer we should target and how we should target them.

ferlin --- myoferlin --- dysferlin --- otoferlin --- C2 domain --- plasma membrane --- sulconazole --- NF-κB --- IL-8 --- mammosphere --- breast cancer stem cells --- AF1Q --- MLLT11 --- WNT --- STAT --- esophageal cancer --- prognosis --- mTORC1 --- mTORC2 --- metabolism --- rapalogs --- mTOR inhibitors --- cancer metabolism --- mTOR in immunotherapy --- nutrient metabolism --- kinase inhibitors --- mTOR signaling --- MAPK kinase --- ERK1 --- ERK2 --- CD domain --- Rolled --- SCH772984 --- VRT-11E --- sevenmaker --- cancer therapy --- EMT --- lysosome --- lysosome-mediated invasion --- MZF1 --- phosphorylation --- PAK4 --- SUMOylation --- transcription factor --- zinc finger --- glucocorticoids --- 3D growth --- nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) --- epithelial–mesenchymal transition --- anoikis --- proliferation --- targeted cancer therapy --- disulfiram --- NPL4 --- replication stress --- DNA damage --- BRCA1 --- BRCA2 --- ATR pathway --- PDAC --- TCIRG1 --- ATP6V0a3 --- invasion --- migration --- matrix degradation --- pH-regulation --- autophagy --- multidrug resistance in cancer --- drug efflux pumps --- ATP-binding cassette transporter --- breast cancer resistance protein (BCRP) --- ABCG2 --- pyrazolo-pyrimidine derivative --- SCO-201 --- colorectal cancer --- immunotherapy --- inflammation --- microsatellite instability --- oncofetal chondroitin sulfate --- chondroitin sulfate --- cancer --- solid tumors --- target --- pediatric cancer --- VAR2 --- dexamethasone --- thyroid cancer --- microgravity --- space environment --- n/a --- epithelial-mesenchymal transition

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The cancer stem cell (CSC) paradigm represents one of the most prominent breakthroughs of the last decades in tumor biology. CSCs are that subpopulation within a tumor that can survive conventional therapies and as a consequence are able to fuel tumor recurrence. Nevertheless, the biological characteristics of CSCs and even their existence, remain the main topic among tumor biologists debates. The difficulty in achieving a better definition of CSC biology may actually be explained by the plasticity of such a cell subpopulation. Indeed, the emerging view is that CSCs represent a dynamic “state” of tumor cells that can acquire stemness-related properties under specific circumstances, rather than referring to a well-defined group of cells. Regardless of their origin, it is clear that designing novel antitumor treatments based on the eradication of CSCs will only be possible upon unraveling the biological mechanisms that underlie their pathogenic role in tumor progression and therapy resistance. The Special Issue on “New aspects of cancer stem cell biology: implications for innovative therapies” aims at highlighting recent insights into CSC features that can make them an attractive target for novel therapeutic strategies.

Cadherin 11 --- WNT signaling --- β-catenin --- cancer stem cells --- TNBC --- early breast cancer --- bevacizumab --- neoadjuvant chemotherapy --- ALDH1 --- solid cancer --- chemo-resistance --- HDAC inhibitors --- head and neck squamous cell carcinoma --- SRC --- dasatinib --- saracatinib --- EC-8042 --- Ovarian cancer --- Wnt signaling --- tumor progression --- therapy resistance --- exosomes --- oral cancer risk --- oral epithelial dysplasia --- SOX2 --- immunohistochemistry --- oral squamous cell carcinoma --- genome-wide --- transcriptome --- lung cancer --- ATAC-seq --- RNA-seq --- CSCs --- NSCLC --- B4GALT1 --- LUAD --- breast cancer --- lipid --- metabolism --- therapeutic resistance --- bowel cancer --- organoid --- tumoroid --- colorectal --- colon --- stem cell --- chemotherapy resistance --- ovarian cancer --- cancer stem cell --- genetic heterogeneity --- SNP array --- L1CAM --- chemoresistance --- epithelial-mesenchymal transition --- cancer therapy --- cell adhesion molecule

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The analysis of circulating tumor cells (CTCs) as a real-time liquid biopsy approach can be used to obtain new insights into metastasis biology, and as companion diagnostics to improve the stratification of therapies and to obtain insights into the therapy-induced selection of cancer cells. In this book, we will cover all the different facets of CTCs to assemble a huge corpus of knowledge on cancer dissemination: technologies for their enrichment, detection, and characterization; their analysis at the single-cell level; their journey as CTC microemboli; their clinical relevance; their biology with the epithelial-to-mesenchymal transition (EMT); their stem-cell properties; their potential to initiate metastasis at distant sites; their ex vivo expansion; and their escape from the immune system.

n/a --- FOLFIRINOX --- immunofluorescence imaging --- AR-V7 --- circulating tumour cells --- chemoradioresistance --- CTC-based treatment decisions --- rVAR2 --- immunophenotyping --- immune system --- CellSearch® --- flow cytometry --- clinical trials --- circulating tumor DNA --- synaptophysin --- stem cells --- colorectal cancer --- melanoma --- CTC biology --- platelets --- AR --- CTC capture technology --- castration resistant prostate cancer (CRPC) --- PD-L1 expression --- rovalpituzumab tesirine --- HMB-45 --- thymidylate synthase --- ctDNA --- tumor cell dissemination --- solid cancers --- metastasis --- locally advanced rectal cancer --- miRNA --- epithelial-to-mesenchymal transition (EMT) --- NSCLC --- tumor biomarkers --- tumor stem cells --- circulating tumor cells --- major histocompatibility complex class I (MHCI) --- bone marrow --- heterogeneity --- cerebrospinal liquid biopsy --- fish --- glioma --- in vivo flow cytometry --- colorectal surgery --- CellSearch --- single-cell analysis --- disseminated tumor cells --- EasyCount slides --- microsatellite instability --- circulating plasma cells --- circulating leukemia cells --- ARV7 --- SLUG --- androgen receptor --- metastatic colorectal cancer --- leukocyte-derived extracellular vesicles --- prostate cancer (PCa) --- neutrophils --- liquid biopsy --- enzalutamide --- CD133 --- enrichment and detection technologies --- biomarkers --- immune checkpoint inhibitors --- biomarker --- RAD23B --- microbiome --- integrin B1 --- ACCEPT --- emboli --- small-cell lung carcinoma --- EPISPOT --- microfluidics --- early breast cancer --- circulating tumor cells (CTC) --- tumor-initiating cells (TICs) --- immunomodulation --- xenograft models --- CTC-derived xenografts --- malaria --- circulating tumor cells (CTCs) --- clinical utility --- exosomes --- liquid surgery --- ctRNA --- CTCs --- epithelial–mesenchymal transition --- targeted therapy --- hematological cells --- gene expression analysis --- hepatocellular carcinoma (HCC) --- breast cancer --- EpCAM enrichment --- prostate cancer --- CTC --- abiraterone --- fibronectin --- CTC-derived ex vivo models --- CTMat --- chromogranin A --- CTM --- exosome --- epithelial-mesenchymal transition

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Cancer of the urological sphere is a disease continuously increasing in numbers in the statistics of tumor malignancies in Western countries. Although this fact is mainly due to the contemporary increase of life expectancy of the people in these geographic areas, many other factors do contribute as well to this growth. Urological cancer is a complex and varied disease of different organs and mainly affects the male population. In fact, kidney, prostate, and bladder cancer are regularly included in the top-ten list of the most frequent neoplasms in males in most statistics. The female population, however, has also increasingly found itself affected by renal and bladder cancer in the last decade. Considering these altogether, urological cancer is a problem of major concern in developed societies. This Topic Issue of Cancers intends to shed some light into the complexity of this field and will consider all useful and appropriate contributions that scientists and clinicians may provide to improve urological cancer knowledge for patients’ benefit. The precise identification of the molecular routes involved, the diagnostic pathological criteria in the grey zones, the dilemma of T1G3 management, and the possible treatment options between superficial, nonmuscle-invasive and muscle-invasive diseases will be particularly welcomed in this Issue.

bladder cancer --- radiotherapy --- radiosensitisation --- molecular subtypes --- preclinical studies --- bladder cancer cell lines --- latent cancer --- prostate cancer --- autopsy --- prognostic index --- prediction model --- mortality --- screening trial --- renal cell carcinoma --- PD-1 --- PD-L1 --- biomarkers --- immune checkpoint inhibitors --- prostatic neoplasms --- positron-emission tomography --- decision making --- tumor thrombus --- metastasectomy --- postoperative complications --- oncological outcomes --- radical cystectomy --- AHNAK2 --- prognosis --- dog --- comparative oncology --- inflammation --- prostatic atrophy --- preneoplastic lesion --- biomarker --- urine --- machine learning --- TRIPOD --- liquid biopsy --- glutaminase --- immunohistochemistry --- in situ methods --- prostate --- PSMA-RLT --- 177Lu-PSMA --- PSA --- mCRPC --- urinary bladder neoplasms --- Bacillus Calmette–Guérin (BCG) --- immunotherapy --- divergent differentiation --- variant morphology --- survival --- stereotactic body radiotherapy --- frail patients --- cancer --- metastasis --- genomic analysis --- microenvironment --- tumor ecology --- game theory --- fluorescence confocal microscopy --- prostate biopsy --- ablation margins --- focal therapy --- sphingosine 1-phosphate receptor 1 --- bladder carcinoma --- cell migration --- epithelial–mesenchymal transition --- FTY-720 --- OIP5 --- papillary renal cell carcinoma --- PLK1 --- tumorigenesis --- therapy --- image-guided --- magnetic resonance imaging --- ultrasonography --- biopsy --- abiraterone --- enzalutamide --- docetaxel --- novel hormonal therapies --- comparative effectiveness --- real-world treatment pattern --- metastatic prostate cancer --- epiplakin --- diagnosis --- advanced urothelial carcinoma --- immune checkpoint inhibitor --- prognostic --- tumour mutational board --- genomic signatures --- ctDNA --- inflammatory indices --- urothelial carcinoma --- frailty --- prognostic factor --- psoas muscle --- Hounsfield units --- n/a --- Bacillus Calmette-Guérin (BCG) --- epithelial-mesenchymal transition --- Research. --- Chemistry.