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The past decades have seen major developments in the understanding of the cellular and molecular biology of cancer. Significant progress has been achieved regarding long-term survival for the patients of many cancers with the use of tamoxifen for treatment of breast cancer, treatment of chronic myeloid leukaemia with imatinib, and the success of biological drugs. The transition from cytotoxic chemotherapy to targeted cancer drug discovery and development has resulted in an increasing selection of tools available to oncologists. In this Special Issue of Pharmaceuticals, we highlight the opportunities and challenges in the discovery and design of innovative cancer therapies, novel small-molecule cancer drugs and antibody-drug conjugates, with articles covering a variety of anticancer therapies and potential relevant disease states and applications. Significant efforts are being made to develop and improve cancer treatments and to translate basic research findings into clinical use, resulting in improvements in survival rates and quality of life for cancer patients. We demonstrate the possibilities and scope for future research in these areas and also highlight the challenges faced by scientists in the area of anticancer drug development leading to improved targeted treatments and better survival rates for cancer patients.

graphene oxide --- indole --- androgens --- cyclooxygenase-2 --- cyclooxygenase-1 --- heteropolysaccharide --- drug conjugation --- drug delivery --- ellipticine --- chemical linker --- oesophageal cancer --- antiproliferative activity --- topoisomerase II --- ?-lactam --- DSD --- antibody --- topoisomerase inhibitors --- magnetic targeting --- cisplatin resistance --- steroidogenesis --- [18F]FDG PET/CT --- heterocyclic chemistry --- dehydroepiandrosterone --- antimitotic --- 3-vinylazetidin-2-ones --- glioblastoma --- and cancer therapy --- intestinal mucositis --- Combretastatin A-4 --- metabolism --- anti-cancer drugs --- maghemite --- COX-1 inhibitor --- anticancer --- CYP17A1 --- conjugate and hybrid drugs --- inflammation --- snticancer drugs --- P450c17 --- tumorigenesis --- cisplatin --- biomarker profiling --- cancer drug design --- tubulin --- cytochrome P450 --- 5-fluorouracil --- prostate cancer --- abiraterone --- NCI screen --- radiation --- cancer immunotherapy --- microtubule targeted drugs --- cancer --- treatment resistance

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The cooperation of highly specialized cell types maintains the homeostasis of multicellular organisms. The disturbance of that harmony contributes to the development of several diseases. Most of the cellular functions are executed by proteins, so it is essential to investigate biological processes at the protein level. Antibodies, complex biomolecules with high specificity, are used to recognize our protein of interest in a process known as “immunophenotyping”. One of the routinely used methods to study cellular proteins is flow cytometry, which detects cell surface or intracellular proteins at single-cell resolution. The other most frequent technique is the traditional immunohistochemical investigation of microscopic sections of human tissues. We called authors to publish their latest data studying cancer or autoimmune diseases by immunophenotyping.

CD8+CD28− T cells --- cancer immunology --- glioblastoma --- immunotherapy --- malignant glioma --- cancer --- accidental cell death --- oncosis --- DDR --- parthanatos --- flow cytometry --- systemic lupus erythematosus --- T cells --- glycosylation --- sialylation --- lectin binding --- glycosylation enzymes --- galectin 1 --- choriocarcinoma --- hydatidiform mole --- galectin --- gestational trophoblastic disease --- placental-specific gene --- systems biology --- trophoblast differentiation --- B cells --- non-switched B cells --- systemic sclerosis --- dcSSc --- TLR --- CD180 --- RP105 --- CpG --- IL-6 --- IL-10 --- natural autoantibodies --- IgM --- citrate synthase --- DNA topoisomerase I --- unfolded protein response --- Inositol-requiring enzyme 1 (IRE1) --- PKR-like endoplasmic reticulum kinase (PERK) --- Glucose-regulated protein 78 (GRP78) --- Activating transcription factor 6 (ATF6) --- immune cells --- T cell --- macrophage --- tumor microenvironment --- single cell mass cytometry --- metastatic breast cancer --- myeloid-derived suppressor cells --- immunophenotyping --- breast cancer --- trastuzumab --- chimeric antigen receptor --- cell therapy --- neuroendocrine neoplasia --- neuroendocrine tumor --- neuroendocrine carcinoma --- immunohistochemistry --- syntaxin 1

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This book is conceived to promote synergy between research and industrial activities in the design and development of new drugs and, therefore, is not limited to any specific aspect of development. It covers the entire process from the identification of a molecular target, studies of drug–protein interactions, the modeling and optimization of the functional activity, design and chemical synthesis, biological evaluation, and the development of new pharmaceutical carriers.The original articles and reviews are focused on the design and development of new anticancer treatments, new anticancer low-molecular-weight agents as potential drug substances, and the elucidation of their mechanisms of action. The book also includes studies on novel modulators of the serotonergic system used to treat central nervous system disorders, novel agents against infectious diseases, and the development of anti-plasmodial and anti-inflammatory agents. The successful identification of new compounds for development as drug substances comes from rich sources of medicinal plants and medicinal chemistry approaches.

alpha-ketoglutarate --- cell cycle --- apoptosis --- JNK --- cell migration --- cell invasion --- TGF-β --- VEGF --- glycoconjugates --- methotrexate --- cancer treatment --- glucose metabolism --- drug design and discovery --- anticancer drugs --- targeted therapy --- Warburg effect --- antidepressants --- pyrido[1,2-c]pyrimidines --- dual 5-HT1A/SERT activity --- drug design --- anticancer activity --- lung cancer --- resveratrol --- PRI-2191 --- vitamin D --- active substance delivery systems --- biomedical hydrogels --- active substance-controlled release --- genistein --- hydrogels for cosmetology --- hydrogels for dermatology --- transdermal active substance delivery systems --- histone deacetylase (HDAC) --- depression --- biomarker --- anti-depressant therapy --- human DNA topoisomerase --- cancer --- drug --- molecular docking --- synthesis --- fluorine --- vitamin D3 --- metabolite --- A-ring --- CD-ring --- side-chain --- nanoparticles --- molecular modeling --- oxidation mechanisms --- electrochemistry --- MALDI --- spectroscopic data --- cytotoxic study --- self-assembled monolayer --- gold electrode --- multimodal activity --- calcium-sensing receptor --- enantiomer --- calcimimetic --- calcilytic --- colon cancer --- stereospecificity --- HT-29 --- IL-8 --- inflammation --- cyclooxygenase --- 1,2,4-triazole --- pyridazinone --- SAR --- anti-inflammatory activity --- antioxidant activity --- ADME --- anticancer drug --- antimicrobial peptide (AMP) --- dermaseptin --- frog skin peptides --- LHRH --- prostate cancer --- Phyllomedusa bicolor --- therapeutic peptides --- copper (II) complexes --- thiourea --- cytotoxic activity --- proteome analysis --- antimicrobial activity --- major latex protein --- Chelidonium majus --- greater celandine --- defense-related proteins --- alkaloids --- cancer cells --- vitamin D receptor --- split luciferase-based biosensor --- CYP24A1-dependent metabolism --- CYP27B1 --- rickets --- genome editing --- vitamin D biology and action --- transcription --- ChIP-chip analysis --- distal enhancers --- histone H3 acetylation --- RNA polymerase II --- analogue actions at genes --- vitamin D hormone (1,25(OH)2D3) --- latex --- antiviral proteins --- antimicrobial compounds --- cytotoxicity --- drug discovery --- CRISPR/Cas9 --- tetrahydro-β-carbolines --- Plasmodium falciparum (P. falciparum) --- antimalarial --- antiparasitic agents --- hemolysis --- vitamin D analogs --- 25 vitamin D 24-hydroxylase --- CYP24A1 --- proliferation --- high-grade serous ovarian cancer cells --- gold --- Au(III) complex --- colorectal cancer --- organometallic --- cancer therapy --- metallodrugs --- n/a

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The very first marine-derived anticancer drug, Cytarabine (aka Ara-C, Cytosar-U®), was approved by the FDA in 1969 for the treatment of leukemia. At the beginning of 2021, the list of approved marine-derived anticancer drugs consists of nine substances, five of which received approval within the last two years, demonstrating the rapid evolution of the field. The current book is a collection of scientific articles related to the exponentially growing field of anticancer marine compounds. These articles cover the whole field, from agents with cancer-preventive activity, to novel and previously characterized compounds with anticancer activity, both in vitro and in vivo, as well as the latest status of compounds under clinical development.

apoptosis --- fucoidan --- hepatocellular carcinoma --- reactive oxygen species --- 3-alkylpyridinium polymers --- nicotine --- nicotinic acetylcholine receptor --- non-small cell lung carcinoma --- melanoma --- sinulariolide --- proteomic --- mitochondria --- caspase cascade --- marine fungus --- sediment --- anthranilic acid --- Penicillium paneum --- cytotoxicity --- dibromotyrosine --- mitochondrial dysfunction --- oxidative stress --- topoisomerase --- epigonal organ --- bonnethead shark --- Jurkat --- tumor cell line --- hippuristanol --- PEL --- AP-1 --- STAT3 --- Akt --- colorectal cancer --- marine mollusc --- brominated indoles --- shrimp --- chemoprevention --- fatty acids --- carotenoids --- cancer --- nanoparticle --- osteosarcoma --- lung metastasis --- elisidepsin --- lipid rafts --- hydroxylated lipids --- fatty acid 2-hydroxylase --- cooperative binding --- membrane permeabilization --- marine organisms --- polysaccharides --- anticancer --- anticarcinogenic --- mechanisms of action --- fumigaclavine C --- anti-proliferation --- mitochondrial pathway --- anti-cancer --- anti-proliferative --- carotenoid --- cell cycle arrest --- fucoxanthin --- azoxymethane --- bioactive natural product --- isatin --- in vivo model --- Marthasterias glacialis L. --- palmitic acid --- ER-stress --- CHOP --- Antibody Drug Conjugates (ADCs) --- marine antitumor agents --- clinical trials --- approved antitumor agents --- AD0157 --- angiogenesis --- marine drug --- pyrrolidinedione --- secondary metabolites --- cancer preventive --- chemopreventive --- trabectedin --- plitidepsin --- tumor-associated macrophages --- tumor microenvironment --- preclinical --- anticancer immunity --- antiangiogenesis --- fascaplysin --- cyclin-dependent kinase --- small cell lung cancer --- camptothecin --- poly(ADP-ribose)-polymerase inhibitor --- breast cancer --- seaweed --- therapeutic compounds --- autophagy --- marine drugs --- autophagy inhibitors --- autophagy inducers --- macrolide --- programmed cell death --- energy stress --- araguspongine C --- c-Met --- HER2 --- gemcitabine --- pazopanib --- phase I --- safety --- soft tissue sarcoma --- pachastrissamine --- jaspine B --- carbocyclic analogue --- sphingosine kinase inhibitor --- molecular modeling --- ET-743 --- DNA minor groove binder --- chemotherapy --- bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) --- anti-metastatic activity --- cell adhesion --- β1-integrin --- FAK --- BEL-7402 cell --- triterpene glycosides --- sea cucumbers --- antitumor activities --- arrest of cell cycle --- antibacterial --- marangucyclines --- deep-sea --- Streptomyces sp. SCSIO 11594 --- LS-1 --- SNU-C5/5-FU --- TGF-β signaling --- carcinoembryonic antigen --- kalkitoxin --- Moorea producens --- mitochondria toxin --- VEGF --- angiogenesis inhibitor --- hypoxia-inducible factor-1 --- HIF-1 --- Lyngbya majuscula --- marine metabolites --- SZ-685C --- nonfunctioning pituitary adenomas --- Ecklonia cava --- phlorotannins --- dieckol --- migration --- sipholenol A --- ABC transporter --- multidrug resistance --- P-gp/ABCB1 --- BCRP/ABCG2 --- MRP1/ABCC1 --- marine natural products --- glioblastoma --- xyloketal B --- proliferation --- TRPM7 --- marine compound --- ribosomal protein genes --- snoRNA --- FAU --- RPS30 --- SNORA62 --- evolution --- Porifera --- n/a --- Penicillium brevicompactum --- Brevianamide --- Mycochromenic acid derivative --- antifouling --- Caribbean sponge --- plakortide --- endoperoxide --- leukemia --- multi-drug resistant leukemia --- Sarcophyton ehrenbergi --- soft coral --- terpenes --- cembranoids --- cytotoxic activity --- molecular docking --- uveal melanoma --- virtual screening --- Topo I inhibitor --- low toxic --- natural product --- Ulva fasciata --- selenium-containing polysaccharide-protein complex --- pseudopterosin --- NF-κB --- p65 --- inflammation --- cytokine release --- IL-6 --- TNFα --- MCP-1 --- glucocorticoid receptor --- paulomycins --- Micromonospora --- antitumor --- Cantabrian Sea-derived actinobacteria --- puupehenones --- sponges --- antiangiogenic --- antitumoral --- porifera/sponge --- cancer genes --- molecular oncology --- bromophenol --- molecular mechanisms --- cell cycle --- PI3K/Akt --- p38/ERK --- ROS --- human lung cancer --- glycosaminoglycans --- antiproliferative --- heparan sulphate --- gliotoxin --- NSCLC --- adriamycin resistance --- Sepia ink polysaccharides --- antitumour --- chemosensitization --- anticoagulation --- sea anemone --- drug discovery --- endothelial cells --- RGD motif --- kunitz type inhibitor --- prostate cancer --- antioxidant --- natural marine compounds --- marine biotechnology --- microalgae --- marine sponges --- Aeroplysinin --- Isofistularin --- pheochromocytoma and paraganglioma --- metastasis --- cancer progression --- cell adhesion molecules --- integrin β1 --- hypoxia --- phycocyanin --- non-small cell lung cancer --- NF-κB signaling --- marine-derived drugs --- bioanalysis --- chromatography --- manzamine A --- epithelial–mesenchymal transition --- lung cancer --- circulating tumor cells --- signal transduction --- cisplatin --- Lampetra morii --- buccal gland --- cystatin F --- anti-angiogenesis --- cystatin superfamily --- Antimicrobial peptide (AMP) --- Tilapia piscidin 4 (TP4) --- non-small cell lung cancer (NSCLC) --- itampolin A --- FBDD --- p38α --- novel inhibitor --- tetracenomycin X --- cyclin D1 --- proteasomal degradation --- p38 --- c-JUN --- λ-carrageenan --- heparanase --- anticoagulant --- depolymerisation --- cell migration --- Aspergillus --- naphthopyrones --- endophytic fungus --- Leathesia nana --- mangrove-derived actinomycete --- ansamycins --- divergolides --- apoptosis-inducing activity --- actinomycin --- EMT --- invasion --- low molecular weight fucoidan extract --- N-Ras --- neuroblastoma-rat sarcoma --- Cancer --- programmed cell death-ligand 1 --- programmed cell death-ligand 2 --- human sarcoma cell line (HT1080 cells) --- human normal diploid fibroblast (TIG-1 cells) --- chimera --- chemical conjugation --- anticancer agent --- hybridization --- α9-nicotinic acetylcholine receptors (nAChRs) --- breast cancer cells --- αO-conotoxin GeXIVA --- targeted therapy --- gorgonian --- Leptogorgia --- humulane sesquiterpenoids --- anticancer activity --- 12-deacetyl-12-epi-scalaradial --- HeLa cells --- Nur77 --- MAPK/ERK pathway --- Mycalin A --- C15 acetogenins --- synthetic analogues --- antiproliferative activity --- A375 and HeLa cell lines --- polyoxygenated steroids --- sponge --- Haliclona gracilis --- Thalassia testudinum --- thalassiolin B --- polyphenols --- CYP1A1 --- benzo[a]pyrene --- JNK1/2 --- natural products --- synergism --- A549 cells --- cytoskeleton --- P2X7 receptor --- pollution --- anti-angiogenic --- gene expression --- HSP90 --- inhibitor --- epithelial-mesenchymal transition