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Gastrointestinal cancers, such as esophageal and gastric cancers, pancreatic cancers, hepatobiliary cancers, colorectal cancers and gastrointestinal stromal tumors, are frequently diagnosed at an advanced stage and have a dismal prognosis. Even in patients with potentially curative cancer, nearly 50\% will develop recurrent disease despite aggressive treatments. A number of biomarkers currently guide treatment decisions for patients with gastrointestinal neoplasms. Major technological advances in genomics have made it possible to identify critical genetic alterations in cancer, furthering oncology along the path to “personalized cancer medicine”. Future research efforts will focus on the identification of new biomarkers, moving existing biomarkers into earlier lines of therapy and evaluating new combinations of existing biomarkers and therapies.The aim of this Special Issue is to provide an overview of exciting new research in the area of gastrointestinal tumors that may establish innovative personalized management and precision medicine modalities for individualized care.

Medicine --- Pharmacology --- neutrophil-to-lymphocyte ratio --- lymphocyte-to-monocyte ratio --- prognosis --- rectal cancer --- mesorectum --- sphincter preserving --- molecular oncology --- precision medicine --- colorectal cancer --- targeted therapy --- molecular profiling --- pancreatic cysts --- thermal liquid biopsy --- differential scanning calorimetry --- diagnosis --- generalized linear models --- gene signature --- mRNA expression --- VANGL1 --- FFPE --- neurotoxicity --- oxaliplatin --- chemotherapy-induced peripheral neuropathy --- biomarker --- genomics --- neuropathy --- FOLFOX --- FOLFIRINOX --- XELOX --- gastrointestinal cancer --- LAG-3 --- immune checkpoint --- colon cancer --- survival --- microsatellite instability --- immunotherapy --- n/a

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Gastrointestinal cancers, such as esophageal and gastric cancers, pancreatic cancers, hepatobiliary cancers, colorectal cancers and gastrointestinal stromal tumors, are frequently diagnosed at an advanced stage and have a dismal prognosis. Even in patients with potentially curative cancer, nearly 50\% will develop recurrent disease despite aggressive treatments. A number of biomarkers currently guide treatment decisions for patients with gastrointestinal neoplasms. Major technological advances in genomics have made it possible to identify critical genetic alterations in cancer, furthering oncology along the path to “personalized cancer medicine”. Future research efforts will focus on the identification of new biomarkers, moving existing biomarkers into earlier lines of therapy and evaluating new combinations of existing biomarkers and therapies.The aim of this Special Issue is to provide an overview of exciting new research in the area of gastrointestinal tumors that may establish innovative personalized management and precision medicine modalities for individualized care.

Medicine --- Pharmacology --- neutrophil-to-lymphocyte ratio --- lymphocyte-to-monocyte ratio --- prognosis --- rectal cancer --- mesorectum --- sphincter preserving --- molecular oncology --- precision medicine --- colorectal cancer --- targeted therapy --- molecular profiling --- pancreatic cysts --- thermal liquid biopsy --- differential scanning calorimetry --- diagnosis --- generalized linear models --- gene signature --- mRNA expression --- VANGL1 --- FFPE --- neurotoxicity --- oxaliplatin --- chemotherapy-induced peripheral neuropathy --- biomarker --- genomics --- neuropathy --- FOLFOX --- FOLFIRINOX --- XELOX --- gastrointestinal cancer --- LAG-3 --- immune checkpoint --- colon cancer --- survival --- microsatellite instability --- immunotherapy

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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.

Medicine --- 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

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Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors.

clear cell renal cell carcinoma --- tumor evolution --- tumor ecology --- intratumor heterogeneity --- multisite tumor sampling --- targeted therapy --- uterine carcinosarcoma --- endometrial carcinoma --- metaplastic carcinoma --- epithelial-to-mesenchymal transition --- clonality --- mutation --- TP53 --- PI3K/AKT pathway --- gene expression --- miRNA expression --- tumor microenvironment --- interstitial pH --- acidosis --- tumor heterogeneity --- magnetic resonance imaging --- hyperpolarized 13C MRI --- carbonic anhydrase --- lactic acid --- positron emission tomography --- esophageal squamous cell carcinoma --- precision medicine --- natural killer cells --- tumor mutation burden --- immunotherapy --- PET --- heterogeneity --- radiomics --- radiopharmaceuticals --- SUV --- nuclear medicine --- colon cancer --- Wnt signaling --- phenotypic plasticity --- EMT --- hybrid E/M --- collective and single-cell migration --- beta-catenin paradox --- breast cancer --- immune microenvironment --- DCIS --- ADH --- mammary gland --- cell fate --- 3D cultures --- organoids --- signaling --- single-cell RNAseq --- tumor endothelial cell --- metastasis --- angiocrine factor --- microsatellite instability --- colorectal cancer --- immune checkpoints --- deficient mismatch repair --- plasticity --- biomechanics --- circulating tumor cells (CTCs) --- extracellular vesicles --- metastatic niche --- epigenetics --- CTC-clusters --- single-cell analysis --- cellular heterogeneity --- circulating tumor cells --- pancreatic cancer --- epithelial mesenchymal plasticity --- target discovery --- review --- genomics --- intra-tumour heterogeneity --- subclonal diversity --- treatment resistance

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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.

Research & information: general --- Biology, life sciences --- 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