1 4769 142 NUCLEAR MORPHOMETRY, NUCLEOMICS AND PROSTATE CANCER PROGRESSION. PROSTATE CANCER (PCA) RESULTS FROM A MULTISTEP PROCESS. THIS PROCESS INCLUDES INITIATION, WHICH OCCURS THROUGH VARIOUS AGING EVENTS AND MULTIPLE INSULTS (SUCH AS CHRONIC INFECTION, INFLAMMATION AND GENETIC INSTABILITY THROUGH REACTIVE OXYGEN SPECIES CAUSING DNA DOUBLE-STRAND BREAKS), FOLLOWED BY A MULTISTEP PROCESS OF PROGRESSION. THESE STEPS INCLUDE SEVERAL GENETIC AND EPIGENETIC ALTERATIONS, AS WELL AS ALTERATIONS TO THE CHROMATIN STRUCTURE, WHICH OCCUR IN RESPONSE TO THE CARCINOGENIC STRESS-RELATED EVENTS THAT SUSTAIN PROLIFERATIVE SIGNALING. EVENTS SUCH AS EVADING GROWTH SUPPRESSORS, RESISTING CELL DEATH, ENABLING REPLICATIVE IMMORTALITY, INDUCING ANGIOGENESIS, AND ACTIVATING INVASION AND METASTASIS ARE READILY OBSERVED. IN ADDITION, IN CONJUNCTION WITH THESE CRITICAL DRIVERS OF CARCINOGENESIS, OTHER FACTORS RELATED TO THE ETIOPATHOGENESIS OF PCA, INVOLVING ENERGY METABOLISM AND EVASION OF THE IMMUNE SURVEILLANCE SYSTEM, APPEAR TO BE INVOLVED. IN ADDITION, WHEN CANCER SPREAD AND METASTASIS OCCUR, THE 'TUMOR MICROENVIRONMENT' IN THE BONE OF PCA PATIENTS MAY PROVIDE A WAY TO SUSTAIN DORMANCY OR SENESCENCE AND EVENTUALLY ESTABLISH A 'SEED AND SOIL' SITE WHERE PCA PROLIFERATION AND GROWTH MAY OCCUR OVER TIME. WHEN PCA IS INITIATED AND PROGRESSION ENSUES, SIGNIFICANT ALTERATIONS IN NUCLEAR SIZE, SHAPE AND HETEROCHROMATIN (DNA TRANSCRIPTION) ORGANIZATION ARE FOUND, AND KEY NUCLEAR TRANSCRIPTIONAL AND STRUCTURAL PROTEINS, AS WELL AS MULTIPLE NUCLEAR BODIES CAN LEAD TO PRECANCEROUS AND MALIGNANT CHANGES. THESE SERIES OF CELLULAR AND TISSUE-RELATED MALIGNANCY-ASSOCIATED EVENTS CAN BE QUANTIFIED TO ASSESS DISEASE PROGRESSION AND MANAGEMENT. 2012 2 6428 34 THE TUMOR MICROENVIRONMENT AND METASTATIC DISEASE. THE MICROENVIRONMENT OF SOLID TUMORS IS A HETEROGENEOUS, COMPLEX MILIEU FOR TUMOR GROWTH AND SURVIVAL THAT INCLUDES FEATURES SUCH AS ACIDIC PH, LOW NUTRIENT LEVELS, ELEVATED INTERSTITIAL FLUID PRESSURE (IFP) AND CHRONIC AND FLUCTUATING LEVELS OF OXYGENATION THAT RELATE TO THE ABNORMAL VASCULAR NETWORK THAT EXISTS IN TUMORS. THE METASTATIC POTENTIAL OF TUMOR CELLS IS BELIEVED TO BE REGULATED BY INTERACTIONS BETWEEN THE TUMOR CELLS AND THEIR EXTRACELLULAR ENVIRONMENT (EXTRACELLULAR MATRIX (ECM)). THESE INTERACTIONS CAN BE MODIFIED BY THE ACCUMULATION OF GENETIC CHANGES AND BY THE TRANSIENT ALTERATIONS IN GENE EXPRESSION INDUCED BY THE LOCAL TUMOR MICROENVIRONMENT. CLINICAL AND EXPERIMENTAL EVIDENCE SUGGESTS THAT ALTERED GENE EXPRESSION IN RESPONSE TO THE HYPOXIC MICROENVIRONMENT IS A CONTRIBUTING FACTOR TO INCREASED METASTATIC EFFICIENCY. A NUMBER OF GENES THAT HAVE BEEN IMPLICATED IN THE METASTATIC PROCESS, INVOLVING ANGIOGENESIS, INTRA/EXTRAVASATION, SURVIVAL AND GROWTH, HAVE BEEN FOUND TO BE HYPOXIA-RESPONSIVE. THE VARIOUS METASTATIC DETERMINANTS, GENETIC AND EPIGENETIC, SOMATIC AND INHERITED MAY SERVE AS PRECEDENTS FOR THE FUTURE IDENTIFICATION OF MORE GENES THAT ARE INVOLVED IN METASTASIS. MUCH RESEARCH HAS FOCUSED ON GENETIC AND MOLECULAR PROPERTIES OF THE TUMOR CELLS THEMSELVES. IN THE PRESENT REVIEW WE DISCUSS THE EPIGENETIC AND PHYSIOLOGICAL REGULATION OF METASTASIS AND EMPHASIZE THE NEED FOR FURTHER STUDIES ON THE INTERACTIONS BETWEEN THE PATHOPHYSIOLOGIC TUMOR MICROENVIRONMENT AND THE TUMOR EXTRACELLULAR MATRIX. 2009 3 6201 34 THE INFLAMMATORY MICROENVIRONMENT AND MICROBIOME IN PROSTATE CANCER DEVELOPMENT. CHRONIC INFLAMMATION PROMOTES THE DEVELOPMENT OF SEVERAL TYPES OF SOLID CANCERS AND MIGHT CONTRIBUTE TO PROSTATE CARCINOGENESIS. THIS HYPOTHESIS PARTLY ORIGINATES IN THE FREQUENT OBSERVATION OF INFLAMMATORY CELLS IN THE PROSTATE MICROENVIRONMENT OF ADULT MEN. INFLAMMATION IS ASSOCIATED WITH PUTATIVE PROSTATE CANCER PRECURSOR LESIONS, TERMED PROLIFERATIVE INFLAMMATORY ATROPHY. INFLAMMATION MIGHT DRIVE PROSTATE CARCINOGENESIS VIA OXIDATIVE STRESS AND GENERATION OF REACTIVE OXYGEN SPECIES THAT INDUCE MUTAGENESIS. ADDITIONALLY, INFLAMMATORY STRESS MIGHT CAUSE EPIGENETIC ALTERATIONS THAT PROMOTE NEOPLASTIC TRANSFORMATION. PROLIFERATIVE INFLAMMATORY ATROPHY IS ENRICHED FOR PROLIFERATIVE LUMINAL EPITHELIAL CELLS OF INTERMEDIATE PHENOTYPE THAT MIGHT BE PRONE TO GENOMIC ALTERATIONS LEADING TO PROSTATIC INTRAEPITHELIAL NEOPLASIA AND PROSTATE CANCER. STUDIES IN ANIMALS SUGGEST THAT INFLAMMATORY CHANGES IN THE PROSTATE MICROENVIRONMENT CONTRIBUTE TO REPROGRAMMING OF PROSTATE EPITHELIAL CELLS, A POSSIBLE STEP IN TUMOUR INITIATION. PROSTATIC INFECTION, CONCURRENT WITH EPITHELIAL BARRIER DISRUPTION, MIGHT BE A KEY DRIVER OF AN INFLAMMATORY MICROENVIRONMENT; THE DISCOVERY OF A URINARY MICROBIOME INDICATES A POTENTIAL SOURCE OF FREQUENT EXPOSURE OF THE PROSTATE TO A DIVERSE NUMBER OF MICROORGANISMS. HENCE, CURRENT EVIDENCE SUGGESTS THAT INFLAMMATION AND ATROPHY ARE INVOLVED IN PROSTATE CARCINOGENESIS AND SUGGESTS A ROLE FOR THE MICROBIOME IN ESTABLISHING AN INFLAMMATORY PROSTATE MICROENVIRONMENT THAT MIGHT PROMOTE PROSTATE CANCER DEVELOPMENT AND PROGRESSION. 2018 4 2036 36 EPIGENETIC CHANGES OF THE IMMUNE SYSTEM WITH ROLE IN TUMOR DEVELOPMENT. TUMOR DEVELOPMENT IS CLOSELY RELATED TO CHRONIC INFLAMMATION AND TO EVASION OF IMMUNE DEFENSE MECHANISMS BY NEOPLASTIC CELLS. THE MEDIATORS OF THE INFLAMMATORY PROCESS AS WELL AS PROTEINS INVOLVED IN IMMUNE RESPONSE OR IMMUNE RESPONSE EVASION CAN BE SUBJECT TO VARIOUS EPIGENETIC CHANGES SUCH AS METHYLATION, ACETYLATION, OR PHOSPHORYLATION. SOME OF THESE, SUCH AS CYTOKINE SUPPRESSORS, ARE UNDERGOING REPRESSION THROUGH EPIGENETIC CHANGES, AND OTHERS SUCH AS CYTOKINES OR CHEMOKINES ARE UNDERGOING ACTIVATION THROUGH EPIGENETIC CHANGES, BOTH MODIFICATIONS HAVING AS A RESULT TUMOR PROGRESSION. THE ACTIVATING CHANGES CAN AFFECT THE RECEPTOR MOLECULES INVOLVED IN IMMUNE RESPONSE AND THESE PROMOTE INFLAMMATION AND SUBSEQUENTLY TUMOR DEVELOPMENT WHILE THE INACTIVATING CHANGES SEEM TO BE RELATED TO THE TUMOR REGRESSION PROCESS. THE PROTEINS INVOLVED IN ANTIGEN PRESENTATION, AND, THEREFORE IN IMMUNE RESPONSE ESCAPE, SUCH AS CLASSICAL HLA PROTEINS AND RELATED APM (ANTIGEN PRESENTATION MACHINERY) WITH THEIR EPIGENETIC CHANGES CONTRIBUTE TO THE TUMOR DEVELOPMENT PROCESS, EITHER TO TUMOR PROGRESSION OR REGRESSION, DEPENDING ON THE IMMUNE EFFECTOR CELLS THAT ARE IN PLAY. 2018 5 5412 35 REGULATION OF ANTITUMOR IMMUNITY BY INFLAMMATION-INDUCED EPIGENETIC ALTERATIONS. CHRONIC INFLAMMATION PROMOTES TUMOR DEVELOPMENT, PROGRESSION, AND METASTATIC DISSEMINATION AND CAUSES TREATMENT RESISTANCE. THE ACCUMULATION OF GENETIC ALTERATIONS AND LOSS OF NORMAL CELLULAR REGULATORY PROCESSES ARE NOT ONLY ASSOCIATED WITH CANCER GROWTH AND PROGRESSION BUT ALSO RESULT IN THE EXPRESSION OF TUMOR-SPECIFIC AND TUMOR-ASSOCIATED ANTIGENS THAT MAY ACTIVATE ANTITUMOR IMMUNITY. THIS ANTAGONISM BETWEEN INFLAMMATION AND IMMUNITY AND THE ABILITY OF CANCER CELLS TO AVOID IMMUNE DETECTION AFFECT THE COURSE OF CANCER DEVELOPMENT AND TREATMENT OUTCOMES. WHILE INFLAMMATION, PARTICULARLY ACUTE INFLAMMATION, SUPPORTS T-CELL PRIMING, ACTIVATION, AND INFILTRATION INTO INFECTED TISSUES, CHRONIC INFLAMMATION IS MOSTLY IMMUNOSUPPRESSIVE. HOWEVER, THE MAIN MECHANISMS THAT DICTATE THE OUTCOME OF THE INFLAMMATION-IMMUNITY INTERPLAY ARE NOT WELL UNDERSTOOD. RECENT DATA SUGGEST THAT INFLAMMATION TRIGGERS EPIGENETIC ALTERATIONS IN CANCER CELLS AND COMPONENTS OF THE TUMOR MICROENVIRONMENT. THESE ALTERATIONS CAN AFFECT AND MODULATE NUMEROUS ASPECTS OF CANCER DEVELOPMENT, INCLUDING TUMOR GROWTH, THE METABOLIC STATE, METASTATIC SPREAD, IMMUNE ESCAPE, AND IMMUNOSUPPRESSIVE OR IMMUNOSUPPORTIVE LEUKOCYTE GENERATION. IN THIS REVIEW, WE DISCUSS THE ROLE OF INFLAMMATION IN INITIATING EPIGENETIC ALTERATIONS IN IMMUNE CELLS, CANCER-ASSOCIATED FIBROBLASTS, AND CANCER CELLS AND SUGGEST HOW AND WHEN EPIGENETIC INTERVENTIONS CAN BE COMBINED WITH IMMUNOTHERAPIES TO IMPROVE THERAPEUTIC OUTCOMES. 2022 6 6395 45 THE ROLE OF THE MEDIATORS OF INFLAMMATION IN CANCER DEVELOPMENT. EPIGENETIC DISORDERS SUCH AS POINT MUTATIONS IN CELLULAR TUMOR SUPPRESSOR GENES, DNA METHYLATION AND POST-TRANSLATIONAL MODIFICATIONS ARE NEEDED TO TRANSFORMATION OF NORMAL CELLS INTO CANCER CELLS. THESE EVENTS RESULT IN ALTERATIONS IN CRITICAL PATHWAYS RESPONSIBLE FOR MAINTAINING THE NORMAL CELLULAR HOMEOSTASIS, TRIGGERING TO AN INFLAMMATORY RESPONSE WHICH CAN LEAD THE DEVELOPMENT OF CANCER. THE INFLAMMATORY RESPONSE IS A UNIVERSAL DEFENSE MECHANISM ACTIVATED IN RESPONSE TO AN INJURY TISSUE, OF ANY NATURE, THAT INVOLVES BOTH INNATE AND ADAPTIVE IMMUNE RESPONSES, THROUGH THE COLLECTIVE ACTION OF A VARIETY OF SOLUBLE MEDIATORS. MANY INFLAMMATORY SIGNALING PATHWAYS ARE ACTIVATED IN SEVERAL TYPES OF CANCER, LINKING CHRONIC INFLAMMATION TO TUMORIGENESIS PROCESS. THUS, INFLAMMATORY RESPONSES PLAY DECISIVE ROLES AT DIFFERENT STAGES OF TUMOR DEVELOPMENT, INCLUDING INITIATION, PROMOTION, GROWTH, INVASION, AND METASTASIS, AFFECTING ALSO THE IMMUNE SURVEILLANCE. IMMUNE CELLS THAT INFILTRATE TUMORS ENGAGE IN AN EXTENSIVE AND DYNAMIC CROSSTALK WITH CANCER CELLS, AND SOME OF THE MOLECULAR EVENTS THAT MEDIATE THIS DIALOG HAVE BEEN REVEALED. A RANGE OF INFLAMMATION MEDIATORS, INCLUDING CYTOKINES, CHEMOKINES, FREE RADICALS, PROSTAGLANDINS, GROWTH AND TRANSCRIPTION FACTORS, MICRORNAS, AND ENZYMES AS, CYCLOOXYGENASE AND MATRIX METALLOPROTEINASE, COLLECTIVELY ACTS TO CREATE A FAVORABLE MICROENVIRONMENT FOR THE DEVELOPMENT OF TUMORS. IN THIS REVIEW ARE PRESENTED THE MAIN MEDIATORS OF THE INFLAMMATORY RESPONSE AND DISCUSSED THE LIKELY MECHANISMS THROUGH WHICH, THEY INTERACT WITH EACH OTHER TO CREATE A CONDITION FAVORABLE TO DEVELOPMENT OF CANCER. 2015 7 723 40 CAN EPIGENETIC AND INFLAMMATORY BIOMARKERS IDENTIFY CLINICALLY AGGRESSIVE PROSTATE CANCER? PROSTATE CANCER (PCA) IS A HIGHLY PREVALENT MALIGNANCY AND CONSTITUTES A MAJOR CAUSE OF CANCER-RELATED MORBIDITY AND MORTALITY. IT EMERGES THROUGH THE ACQUISITION OF GENETIC AND EPIGENETIC ALTERATIONS. EPIGENETIC MODIFICATIONS INCLUDE DNA METHYLATION, HISTONE MODIFICATIONS AND MICRORNA DEREGULATION. THESE GENERATE HERITABLE TRANSFORMATIONS IN THE EXPRESSION OF GENES BUT DO NOT CHANGE THE DNA SEQUENCE. ALTERATIONS IN DNA METHYLATION (HYPO AND HYPERMETHYLATION) ARE THE MOST CHARACTERIZED IN PCA. THEY LEAD TO GENOMIC INSTABILITY AND INADEQUATE GENE EXPRESSION. MAJOR AND MINOR-SPECIFIC MODIFICATIONS IN CHROMATIN RECASTING ARE INVOLVED IN PCA, WITH SIGNS SUGGESTING A DYSFUNCTION OF ENZYMES MODIFIED BY HISTONES. MICRORNA DEREGULATION ALSO CONTRIBUTES TO THE INITIATION OF PCA, INCLUDING INVOLVEMENT IN ANDROGEN RECEPTOR SIGNALIZATION AND APOPTOSIS. THE INFLUENCE OF INFLAMMATION ON PROSTATE TUMOR CARCINOGENESIS IS CURRENTLY MUCH BETTER KNOWN. RECENT DISCOVERIES ABOUT MICROBIAL SPECIES RESIDENT IN THE URINARY TRACT SUGGEST THAT THESE ARE THE INITIATORS OF CHRONIC INFLAMMATION, PROMOTING PROSTATE INFLAMMATORY ATROPHY AND EVENTUALLY LEADING TO PCA. COMPLETE CHARACTERIZATION OF THE RELATIONSHIP BETWEEN THE URINARY MICROBIOME AND PROSTATIC CHRONIC INFLAMMATION WILL BE CRUCIAL TO DEVELOP PLANS FOR THE PREVENTION OF PCA. THE PREVALENT NATURE OF EPIGENETIC AND INFLAMMATORY ALTERATIONS MAY PROVIDE POTENTIAL BIOMARKERS FOR PCA DIAGNOSIS, TREATMENT DECISIONS, EVALUATION OF PROGNOSIS AND POSTTREATMENT SURVEILLANCE. 2020 8 3672 25 INFLAMMATION AND CANCER: AN ANCIENT LINK WITH NOVEL POTENTIALS. INFECTION AND CHRONIC INFLAMMATION CONTRIBUTE TO ABOUT 1 IN 4 OF ALL CANCER CASES. MEDIATORS OF THE INFLAMMATORY RESPONSE, E.G., CYTOKINES, FREE RADICALS, PROSTAGLANDINS AND GROWTH FACTORS, CAN INDUCE GENETIC AND EPIGENETIC CHANGES INCLUDING POINT MUTATIONS IN TUMOR SUPPRESSOR GENES, DNA METHYLATION AND POST-TRANSLATIONAL MODIFICATIONS, CAUSING ALTERATIONS IN CRITICAL PATHWAYS RESPONSIBLE FOR MAINTAINING THE NORMAL CELLULAR HOMEOSTASIS AND LEADING TO THE DEVELOPMENT AND PROGRESSION OF CANCER. RECENT DISCOVERY OF AN INTERACTION BETWEEN MICRORNAS AND INNATE IMMUNITY DURING INFLAMMATION HAS FURTHER STRENGTHENED THE ASSOCIATION BETWEEN INFLAMMATION AND CANCER. 2007 9 928 29 CHRONIC INFLAMMATION, THE TUMOR MICROENVIRONMENT AND CARCINOGENESIS. CHRONIC INFLAMMATION OFTEN PRECEDES OR ACCOMPANIES A SUBSTANTIAL NUMBER OF CANCERS. INDEED, ANTI-INFLAMMATORY THERAPIES HAVE SHOWN EFFICACY IN CANCER PREVENTION AND TREATMENT. THE EXACT MECHANISMS THAT TURN A WOUND HEALING PROCESS INTO A CANCER PRECURSOR ARE TOPICS OF INTENSE RESEARCH. A PATHOGENIC LINK HAS BEEN IDENTIFIED BETWEEN INFLAMMATORY MEDIATORS, INFLAMMATION RELATED GENE POLYMORPHISMS AND CARCINOGENESIS. ANIMAL MODELS OF CANCER HAVE BEEN INSTRUMENTAL IN DEMONSTRATING THE DIVERSITY OF MECHANISMS THROUGH WHICH EVERY TUMOR COMPARTMENT AND TUMOR STAGE MAY BE AFFECTED BY THE UNDERLYING INFLAMMATORY PROCESS. IN THIS REVIEW, WE FOCUS ON THE INTERACTION BETWEEN CHRONIC INFLAMMATION, TUMOR STEM CELLS AND THE TUMOR MICROENVIRONMENT. WE SUMMARIZE THE PROPOSED MECHANISMS THAT LEAD TO THE RECRUITMENT OF BONE MARROW DERIVED CELLS AND EXPLORE THE GENETIC AND EPIGENETIC ALTERATIONS THAT MAY OCCUR IN INFLAMMATION ASSOCIATED CANCERS. 2009 10 5291 36 PROSTATE CARCINOGENESIS: INSIGHTS IN RELATION TO EPIGENETICS AND INFLAMMATION. PROSTATE CANCER IS A MULTIFACTORIAL DISEASE THAT MAINLY OCCURS DUE TO THE ACCUMULATION OF SOMATIC, GENETIC, AND EPIGENETIC CHANGES, RESULTING IN THE INACTIVATION OF TUMOR-SUPPRESSOR GENES AND ACTIVATION OF ONCOGENES. MUTATIONS IN GENES, SPECIFICALLY THOSE THAT CONTROL CELL GROWTH AND DIVISION OR THE REPAIR OF DAMAGED DNA, MAKE THE CELLS GROW AND DIVIDE UNCONTROLLABLY TO FORM A TUMOR. THE RISK OF DEVELOPING PROSTATE CANCER DEPENDS UPON THE GENE THAT HAS UNDERGONE THE MUTATION. IDENTIFYING SUCH GENETIC RISK FACTORS FOR PROSTATE CANCER POSES A CHALLENGE FOR THE RESEARCHERS. BESIDES GENETIC MUTATIONS, MANY EPIGENETIC ALTERATIONS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS (METHYLATION, ACETYLATION, UBIQUITYLATION, SUMOYLATION, AND PHOSPHORYLATION) NUCLEOSOMAL REMODELING, AND CHROMOSOMAL LOOPING, HAVE SIGNIFICANTLY CONTRIBUTED TO THE ONSET OF PROSTATE CANCER AS WELL AS THE PROGNOSIS, DIAGNOSIS, AND TREATMENT OF PROSTATE CANCER. CHRONIC INFLAMMATION ALSO PLAYS A MAJOR ROLE IN THE ONSET AND PROGRESSION OF HUMAN CANCER, VIA MODIFICATIONS IN THE TUMOR MICROENVIRONMENT BY INITIATING EPITHELIALMESENCHYMAL TRANSITION AND REMODELING THE EXTRACELLULAR MATRIX. IN THIS ARTICLE, THE AUTHORS PRESENT A BRIEF HISTORY OF THE MECHANISMS AND POTENTIAL LINKS BETWEEN THE GENETIC ABERRATIONS, EPIGENETIC CHANGES, INFLAMMATION, AND INFLAMMASOMES THAT ARE KNOWN TO CONTRIBUTE TO THE PROGNOSIS OF PROSTATE CANCER. FURTHERMORE, THE AUTHORS EXAMINE AND DISCUSS THE CLINICAL POTENTIAL OF PROSTATE CARCINOGENESIS IN RELATION TO EPIGENETICS AND INFLAMMATION FOR ITS DIAGNOSIS AND TREATMENT.. 2021 11 3697 33 INFLAMMATORY MARKERS IN CANCER: POTENTIAL RESOURCES. CANCER IS A LEADING CAUSE OF DEATH WORLDWIDE AND A MAJOR BURDEN ON DEVELOPING AND LESS DEVELOPED COUNTRIES OF THE WORLD WITH LIMITED RESOURCES FOR PREVENTION AND EFFECTIVE TREATMENT OF CANCER. ALTHOUGH CANCER IS MULTIFACTORIAL IN ORIGIN, VARIOUS EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES SUGGEST THAT CHRONIC INFLAMMATION HAS AN IMPORTANT ROLE IN ALL STAGES OF CANCER, FROM INITIATION TO PROGRESSION AND EVEN SURVIVAL OF THE PATIENT. INFLAMMATORY PRODUCTS LIKE CYTOKINES, CHEMOKINES, LEUCOCYTES, PROSTAGLANDINS, CYCLOOXYGENASE, REACTIVE OXYGEN AND NITROGEN SPECIES, METALLOPROTEINASE INDUCE GENETIC AND EPIGENETIC CHANGES IN NORMAL CELLS DAMAGING ITS DNA, INHIBITING ITS REPAIR, ALTERING TRANSCRIPTION FACTORS, PREVENTING APOPTOSIS, AND STIMULATING ANGIOGENESIS, AND THUS RESULTING IN CARCINOGENESIS. THUS, THESE INFLAMMATORY MEDIATORS HAVE A POTENTIAL ROLE TO BECOME CANCER BIOMARKERS FOR ALL STAGES OF CANCER AS MANY OF THEM CAN BE MEASURED IN A COST-EFFECTIVE MANNER. HOWEVER, LARGE SCALE PROSPECTIVE TRIALS ARE REQUIRED TO VALIDATE THESE POTENTIAL CANCER BIOMARKERS. NONETHELESS, A TRANSITION FROM POTENTIAL TO PRACTICAL UTILIZATION OF THESE MARKERS WILL BE AN EFFECTIVE TOOL FOR THE AMELIORATION OF CANCER BURDEN AND MORTALITY IN A RESOURCE LIMITED SETTING. 2020 12 4479 42 MOLECULAR PATHOGENESIS OF ORAL SQUAMOUS CELL CARCINOMA: IMPLICATIONS FOR THERAPY. THE DEVELOPMENT OF ORAL SQUAMOUS CELL CARCINOMA (OSCC) IS A MULTISTEP PROCESS REQUIRING THE ACCUMULATION OF MULTIPLE GENETIC ALTERATIONS, INFLUENCED BY A PATIENT'S GENETIC PREDISPOSITION AS WELL AS BY ENVIRONMENTAL INFLUENCES, INCLUDING TOBACCO, ALCOHOL, CHRONIC INFLAMMATION, AND VIRAL INFECTION. TUMORIGENIC GENETIC ALTERATIONS CONSIST OF TWO MAJOR TYPES: TUMOR SUPPRESSOR GENES, WHICH PROMOTE TUMOR DEVELOPMENT WHEN INACTIVATED; AND ONCOGENES, WHICH PROMOTE TUMOR DEVELOPMENT WHEN ACTIVATED. TUMOR SUPPRESSOR GENES CAN BE INACTIVATED THROUGH GENETIC EVENTS SUCH AS MUTATION, LOSS OF HETEROZYGOSITY, OR DELETION, OR BY EPIGENETIC MODIFICATIONS SUCH AS DNA METHYLATION OR CHROMATIN REMODELING. ONCOGENES CAN BE ACTIVATED THROUGH OVEREXPRESSION DUE TO GENE AMPLIFICATION, INCREASED TRANSCRIPTION, OR CHANGES IN STRUCTURE DUE TO MUTATIONS THAT LEAD TO INCREASED TRANSFORMING ACTIVITY. THIS REVIEW FOCUSES ON THE MOLECULAR MECHANISMS OF ORAL CARCINOGENESIS AND THE USE OF BIOLOGIC THERAPY TO SPECIFICALLY TARGET MOLECULES ALTERED IN OSCC. THE RAPID PROGRESS THAT HAS BEEN MADE IN OUR UNDERSTANDING OF THE MOLECULAR ALTERATIONS CONTRIBUTING TO THE DEVELOPMENT OF OSCC IS LEADING TO IMPROVEMENTS IN THE EARLY DIAGNOSIS OF TUMORS AND THE REFINEMENT OF BIOLOGIC TREATMENTS INDIVIDUALIZED TO THE SPECIFIC CHARACTERISTICS OF A PATIENT'S TUMOR. 2008 13 6710 34 VIRAL-INDUCED HUMAN CARCINOGENESIS: AN OXIDATIVE STRESS PERSPECTIVE. ONCOGENIC TRANSFORMATION OCCURS VIA MANY DIFFERENT MECHANISMS. ALTERATIONS IN THE EXPRESSION OF CERTAIN KEY GENES (ONCOGENES AND/OR TUMOR SUPPRESSOR GENES) CONTRIBUTE TO THE DEVELOPMENT OF THE TUMORIGENIC STATE OF UNCONTROLLED CELL PROLIFERATION. TUMOR VIRUSES' STUDIES HAVE CONTRIBUTED OVER THE LAST 2 DECADES SIGNIFICANTLY IN CANCER ETIOLOGY, FIRST BY PROVIDING VALUABLE INFORMATION ON THE MECHANISMS AND DISSECTION OF CELL SIGNALING AND GROWTH CONTROL PATHWAYS AND SECOND BY BEING CAUSATIVE AGENTS OF HUMAN NEOPLASIA. VIRUSES CONTRIBUTE TO THE DEVELOPMENT OF THE NEOPLASTIC STATE THROUGH MANY MECHANISMS: INACTIVATION OF TUMOR SUPPRESSOR GENES, HYPERSTIMULATION OF CELLULAR PROTO-ONCOGENE TRANSCRIPTION, OR BY VIRAL PROTEIN INTERFERENCE WITH THE CELLULAR TRANSCRIPTION, SIGNAL TRANSDUCTION, DNA REPAIR AND APOPTOSIS PATHWAYS AND INDUCTION OF CHRONIC OXIDATIVE STRESS. ON THE OTHER HAND, ONLY RECENTLY RESEARCH HAS PROVIDED EVIDENCE OF THE EPIGENETIC PATHWAY INVOLVEMENT AND ESPECIALLY THE DNA METHYLATION MACHINERY. TO THIS END, BOTH HYPOMETHYLATION-INDUCED ONCOGENIC ACTIVATION AND/OR HYPERMETHYLATION-INDUCED TUMOR SUPPRESSOR GENE SILENCING ARE LINKED WITH VIRAL-INDUCED CARCINOGENESIS. IN THIS REVIEW, WE DISCUSS THE CURRENT STATUS OF KNOWLEDGE ON VIRAL-ASSOCIATED CARCINOGENESIS WITH EMPHASIS ON THE MECHANISMS OF OXIDATIVE STRESS AND DNA DAMAGE INDUCTION IN HUMANS BY VIRUSES AS WELL AS IMPLICATIONS IN CANCER TREATMENT. 2010 14 1150 48 CONNECTION BETWEEN INFLAMMATION AND CARCINOGENESIS IN GASTROINTESTINAL TRACT: FOCUS ON TGF-BETA SIGNALING. INFLAMMATION IS A PRIMARY DEFENSE PROCESS AGAINST VARIOUS EXTRACELLULAR STIMULI, SUCH AS VIRUSES, PATHOGENS, FOODS, AND ENVIRONMENTAL POLLUTANTS. WHEN CELLS RESPOND TO STIMULI FOR SHORT PERIODS OF TIME, IT RESULTS IN ACUTE OR PHYSIOLOGICAL INFLAMMATION. HOWEVER, IF THE STIMULATION IS SUSTAINED FOR LONGER TIME OR A PATHOLOGICAL STATE OCCURS, IT IS KNOWN AS CHRONIC OR PATHOLOGICAL INFLAMMATION. SEVERAL STUDIES HAVE SHOWN THAT TUMORIGENESIS IN THE GASTROINTESTINAL (GI) TRACT IS CLOSELY ASSOCIATED WITH CHRONIC INFLAMMATION, FOR WHICH ABNORMAL CELLULAR ALTERATIONS THAT ACCOMPANY CHRONIC INFLAMMATION SUCH AS OXIDATIVE STRESSES, GENE MUTATIONS, EPIGENETIC CHANGES, AND INFLAMMATORY CYTOKINES, ARE SHARED WITH CARCINOGENIC PROCESSES, WHICH FORMS A CRITICAL CROSS-LINK BETWEEN CHRONIC INFLAMMATION AND CARCINOGENESIS. TRANSFORMING GROWTH FACTOR (TGF)-BETA IS A MULTI-POTENT CYTOKINE THAT PLAYS AN IMPORTANT ROLE IN REGULATION OF CELL GROWTH, APOPTOSIS AND DIFFERENTIATION. MOST IMPORTANTLY, TGF-BETA IS A STRONG ANTI-INFLAMMATORY CYTOKINE THAT REGULATES THE DEVELOPMENT OF EFFECTOR CELLS. TGF-BETA HAS A SUPPRESSIVE EFFECT ON CARCINOGENESIS UNDER NORMAL CONDITIONS BY INHIBITING ABNORMAL CELL GROWTH, BUT ON THE OTHER HAND, MANY GI CANCERS ORIGINATE FROM UNCONTROLLED CELL GROWTH AND DIFFERENTIATION BY GENETIC LOSS OF TGF-BETA SIGNALING MOLECULES OR PERTURBATION OF TGF-BETA ADAPTORS. ONCE A TUMOR HAS DEVELOPED, TGF-BETA EXERTS A PROMOTING EFFECT ON THE TUMOR ITSELF AND STROMAL CELLS TO ENHANCE CELL GROWTH, ALTER THE RESPONSIVENESS OF TUMOR CELLS TO STIMULATE INVASION AND METASTASIS, AND INHIBITED IMMUNE SURVEILLANCE. THEREFORE, NOVEL DEVELOPMENT OF THERAPEUTIC AGENTS TO INHIBIT TGF-BETA-INDUCED PROGRESSION OF TUMOR AND TO RETAIN ITS GROWTH INHIBITORY ACTIVITIES, IN ADDITION TO ANTI-INFLAMMATORY ACTIONS, COULD BE USEFUL IN ONCOLOGY. IN THIS REVIEW, WE DISCUSS THE ROLE OF TGF-BETA IN INFLAMMATION AND CARCINOGENESIS OF THE GI TRACT RELATED TO ABNORMAL TGF-BETA SIGNALING. 2010 15 2335 36 EPIGENETIC REGULATION OF INFLAMMATORY CYTOKINES AND ASSOCIATED GENES IN HUMAN MALIGNANCIES. INFLAMMATION IS A MULTIFACETED DEFENSE RESPONSE OF IMMUNE SYSTEM AGAINST INFECTION. CHRONIC INFLAMMATION HAS BEEN IMPLICATED AS AN IMMINENT THREAT FOR MAJOR HUMAN MALIGNANCIES AND IS DIRECTLY LINKED TO VARIOUS STEPS INVOLVED IN TUMORIGENESIS. INFLAMMATORY CYTOKINES, INTERLEUKINS, INTERFERONS, TRANSFORMING GROWTH FACTORS, CHEMOKINES, AND ADHESION MOLECULES HAVE BEEN ASSOCIATED WITH CHRONIC INFLAMMATION. NUMEROUS CYTOKINES ARE REPORTED TO BE ABERRANTLY REGULATED BY DIFFERENT EPIGENETIC MECHANISMS LIKE DNA METHYLATION AND HISTONE MODIFICATIONS IN TUMOR TISSUES, CONTRIBUTING TO PATHOGENESIS OF TUMOR IN MULTIPLE WAYS. SOME OF THESE CYTOKINES ALSO WORK AS EPIGENETIC REGULATORS OF OTHER CRUCIAL GENES IN TUMOR BIOLOGY, EITHER DIRECTLY OR INDIRECTLY. SUCH REGULATIONS ARE REPORTED IN LUNG, BREAST, CERVICAL, GASTRIC, COLORECTAL, PANCREATIC, PROSTATE, AND HEAD AND NECK CANCERS. EPIGENETICS OF INFLAMMATORY MEDIATORS IN CANCER IS CURRENTLY SUBJECT OF EXTENSIVE RESEARCH. THESE INVESTIGATIONS MAY HELP IN UNDERSTANDING CANCER BIOLOGY AND TO DEVELOP EFFECTIVE THERAPEUTIC STRATEGIES. THE PURPOSE OF THIS PAPER IS TO HAVE A BRIEF VIEW OF THE ABERRANT REGULATION OF INFLAMMATORY CYTOKINES IN HUMAN MALIGNANCIES. 2015 16 733 38 CANCER EPIGENETICS: LINKING BASIC BIOLOGY TO CLINICAL MEDICINE. CANCER EVOLUTION AT ALL STAGES IS DRIVEN BY BOTH EPIGENETIC ABNORMALITIES AS WELL AS GENETIC ALTERATIONS. DYSREGULATION OF EPIGENETIC CONTROL EVENTS MAY LEAD TO ABNORMAL PATTERNS OF DNA METHYLATION AND CHROMATIN CONFIGURATIONS, BOTH OF WHICH ARE CRITICAL CONTRIBUTORS TO THE PATHOGENESIS OF CANCER. THESE EPIGENETIC ABNORMALITIES ARE SET AND MAINTAINED BY MULTIPLE PROTEIN COMPLEXES AND THE INTERPLAY BETWEEN THEIR INDIVIDUAL COMPONENTS INCLUDING DNA METHYLATION MACHINERY, HISTONE MODIFIERS, PARTICULARLY, POLYCOMB (PCG) PROTEINS, AND CHROMATIN REMODELING PROTEINS. RECENT ADVANCES IN GENOME-WIDE TECHNOLOGY HAVE REVEALED THAT THE INVOLVEMENT OF THESE DYSREGULATED EPIGENETIC COMPONENTS APPEARS TO BE EXTENSIVE. MOREOVER, THERE IS A GROWING CONNECTION BETWEEN EPIGENETIC ABNORMALITIES IN CANCER AND CONCEPTS CONCERNING STEM-LIKE CELL SUBPOPULATIONS AS A DRIVING FORCE FOR CANCER. EMERGING DATA SUGGEST THAT ASPECTS OF THE EPIGENETIC LANDSCAPE INHERENT TO NORMAL EMBRYONIC AND ADULT STEM/PROGENITOR CELLS MAY HELP FOSTER, UNDER THE STRESS OF CHRONIC INFLAMMATION OR ACCUMULATING REACTIVE OXYGEN SPECIES, EVOLUTION OF MALIGNANT SUBPOPULATIONS. FINALLY, UNDERSTANDING MOLECULAR MECHANISMS INVOLVED IN INITIATION AND MAINTENANCE OF EPIGENETIC ABNORMALITIES IN ALL TYPES OF CANCER HAS GREAT POTENTIAL FOR TRANSLATIONAL PURPOSES. THIS IS ALREADY EVIDENT FOR EPIGENETIC BIOMARKER DEVELOPMENT, AND FOR PHARMACOLOGICAL TARGETING AIMED AT REVERSING CANCER-SPECIFIC EPIGENETIC ALTERATIONS. 2011 17 3683 37 INFLAMMATION, MICROBIOTA, AND PROSTATE CANCER. CONTEXT: CHRONIC INFLAMMATION OF THE PROSTATE HAS BEEN ASSOCIATED WITH PRENEOPLASTIC LESIONS AND CANCER DEVELOPMENT. MULTIPLE CAUSES HAVE BEEN CONSIDERED FOR CHRONIC INFLAMMATION OF THE PROSTATE. INFLAMMATORY CYTOKINES SUCH AS INTERLEUKINS ARE IMPLICATED IN PROSTATE CARCINOGENESIS AND DEVELOPMENT. OBJECTIVE: TO EVALUATE LITERATURE PUBLISHED ON ETIOLOGICAL FACTORS, URINARY MICROBIOTA, MORPHOLOGICAL FEATURES OF PROLIFERATIVE INFLAMMATORY ATROPHY AND HIGH-GRADE PROSTATE INTRAEPITHELIAL NEOPLASIA, GENETIC POLYMORPHISMS, INFLAMMATORY STRESS, AND CYTOKINE SIGNALING. EVIDENCE ACQUISITION: WE SEARCHED LITERATURE FROM PUBMED FROM 2010 AND ALSO INCLUDED THE MOST IMPORTANT PUBLICATIONS FROM THE PREVIOUS PERIOD. EVIDENCE SYNTHESIS: PROSTATE CANCER INFLAMMATION AND PREMALIGNANT LESIONS HAVE BEEN FREQUENTLY DISCUSSED IN SCIENTIFIC LITERATURE. A LIMITED NUMBER OF MODELS ARE AVAILABLE FOR STUDYING INFLAMMATION AND PREMALIGNANT LESIONS. HOWEVER, MORPHOLOGICAL PATHOLOGY COULD BE COMPLEMENTED BY ANALYSIS OF GENE POLYMORPHISMS IN THESE PATIENTS AND APPROPRIATE FUNCTIONAL STUDIES. CONCLUSIONS: PROSTATITIS COULD BE CAUSED BY BACTERIAL OR VIRAL INFECTIONS, DIETARY COMPOUNDS, AND CHANGES IN TESTOSTERONE:ESTRADIOL RATIO. IN SOME CASES, THE MICROBIOTA CAN EXERT DIRECT EFFECTS ON CANCER DEVELOPMENT. PROSTATE INFLAMMATORY ATROPHY OR HIGH GRADE PROSTATE INTRAEPITHELIAL NEOPLASIA HAVE BEEN ASSOCIATED WITH RESPONSE TO CELLULAR STRESS AND HAVE BEEN DISCUSSED IN CONNECTION TO EARLY CANCER DEVELOPMENT. A LARGE NUMBER OF GENETIC POLYMORPHISMS HAVE BEEN IDENTIFIED IN INFLAMMATORY PROSTATE. GENETIC AND EPIGENETIC ALTERATIONS MAY BE A CONSEQUENCE OF THE PROINFLAMMATORY STRESS IN THE PROSTATE. PROINFLAMMATORY CYTOKINES INTERLEUKIN-6 AND -8 CONTRIBUTE TO PROSTATE MALIGNANCY; HOWEVER, THEIR FUNCTION WAS MORE FREQUENTLY INVESTIGATED IN CANCER TISSUE RATHER THAN IN INFLAMMATION. PATIENT SUMMARY: WE PERFORMED A REVIEW OF RECENT LITERATURE RELATED TO PROSTATE INFLAMMATION, MICROBIOTA, AND PROSTATE CANCER. NEW FUNCTIONAL APPROACHES ARE REQUIRED FOR A BETTER UNDERSTANDING OF THE ROLE OF INFLAMMATION AND CANCER DEVELOPMENT. 2016 18 1864 36 EMERGING AVENUES LINKING INFLAMMATION AND CANCER. THE ROLE OF INFLAMMATION IN CARCINOGENESIS HAS BEEN EXTENSIVELY INVESTIGATED AND WELL DOCUMENTED. MANY BIOCHEMICAL PROCESSES THAT ARE ALTERED DURING CHRONIC INFLAMMATION HAVE BEEN IMPLICATED IN TUMORIGENESIS. THESE INCLUDE SHIFTING CELLULAR REDOX BALANCE TOWARD OXIDATIVE STRESS; INDUCTION OF GENOMIC INSTABILITY; INCREASED DNA DAMAGE; STIMULATION OF CELL PROLIFERATION, METASTASIS, AND ANGIOGENESIS; DEREGULATION OF CELLULAR EPIGENETIC CONTROL OF GENE EXPRESSION; AND INAPPROPRIATE EPITHELIAL-TO-MESENCHYMAL TRANSITION. A WIDE ARRAY OF PROINFLAMMATORY CYTOKINES, PROSTAGLANDINS, NITRIC OXIDE, AND MATRICELLULAR PROTEINS ARE CLOSELY INVOLVED IN PREMALIGNANT AND MALIGNANT CONVERSION OF CELLS IN A BACKGROUND OF CHRONIC INFLAMMATION. INAPPROPRIATE TRANSCRIPTION OF GENES ENCODING INFLAMMATORY MEDIATORS, SURVIVAL FACTORS, AND ANGIOGENIC AND METASTATIC PROTEINS IS THE KEY MOLECULAR EVENT IN LINKING INFLAMMATION AND CANCER. ABERRANT CELL SIGNALING PATHWAYS COMPRISING VARIOUS KINASES AND THEIR DOWNSTREAM TRANSCRIPTION FACTORS HAVE BEEN IDENTIFIED AS THE MAJOR CONTRIBUTORS IN ABNORMAL GENE EXPRESSION ASSOCIATED WITH INFLAMMATION-DRIVEN CARCINOGENESIS. THE POSTTRANSCRIPTIONAL REGULATION OF GENE EXPRESSION BY MICRORNAS ALSO PROVIDES THE MOLECULAR BASIS FOR LINKING INFLAMMATION TO CANCER. THIS REVIEW HIGHLIGHTS THE MULTIFACETED ROLE OF INFLAMMATION IN CARCINOGENESIS IN THE CONTEXT OF ALTERED CELLULAR REDOX SIGNALING. 2012 19 3921 44 LINKING INFLAMMATION TO CELL CYCLE PROGRESSION. RISK OF GASTROINTESTINAL CANCERS IS CLOSELY RELATED TO INCREASED LEVELS OF OXIDANTS IN THE BALANCE BETWEEN OXIDANT AND ANTI-OXIDANT AGENTS. A POSSIBLE EXPLANATION OF THIS EPIDEMIOLOGICAL OBSERVATION IS THE LOCAL LOSS OF THE EPITHELIAL BARRIER FUNCTION WITH A FOCAL INFLAMMATORY RESPONSE. ACCORDINGLY, CHRONIC INFLAMMATORY DISEASES REPRESENT WELL-KNOWN RISK FACTORS FOR CANCER AND, ON THE OTHER HAND, IT IS KNOWN THAT ANTI-INFLAMMATORY AGENTS, DEMULCENTS AND ANTIOXIDANTS MARKEDLY INHIBIT THE DEVELOPMENT OF COLON CANCER IN ANIMAL MODELS AS WELL IN HUMANS. AT MOLECULAR LEVEL A KEY ROLE IN THE PROCESS THAT LINK INFLAMMATION TO CELLULAR TRANSFORMATION SEEMS TO BE PLAYED BY ACTIVATION OF CYCLOOXYGENASE-2 (COX-2) TOGETHER WITH PRODUCTION OF REACTIVE OXYGEN INTERMEDIATE (ROI). BOTH THESE EVENTS HAVE BEEN STRICTLY LINKED WITH CELL PROLIFERATION AND TRANSFORMATION, ALTHOUGH THE INTRACELLULAR PATHWAYS INVOLVED IN THESE PROCESSES ARE STILL NOT COMPLETELY UNDERSTOOD. THE UNCONTROLLED PROLIFERATION, WHICH IS A LANDMARK OF CELLULAR TRANSFORMATION, IS ACCOMPANIED BY THE DEREGULATION OF PROTEINS INVOLVED IN THE CONTROL OF CELL CYCLE CHECKPOINTS. ALTERED EXPRESSION AND FUNCTION OF CYCLOOXYGENASE AND NITRIC OXIDE SYNTHASE SEEM TO INFLUENCE, AMONG OTHERS, THE EXPRESSION OF PROTEINS INVOLVED IN THE REGULATION OF CELL CYCLE PROGRESSION. SIMILARLY, ANTI-INFLAMMATORY AND ANTIOXIDANT AGENTS MAY ALSO ACT ON THE EXPRESSION AND FUNCTION OF SEVERAL CELL CYCLE REGULATING PROTEINS. UNDERSTANDING THE MECHANISMS BY WHICH CHRONIC INFLAMMATION CONTRIBUTES TO GENETIC AND EPIGENETIC CHANGES INVOLVED IN THE REGULATION OF CRITICAL CELL CYCLE CHECKPOINTS MAY HELP TO DEVELOP MORE AND MORE SPECIFIC TREATMENT STRATEGIES FOR REDUCING MALIGNANT TRANSFORMATION OF THESE INFLAMMATORY DISEASES. 2004 20 1232 35 CROSSTALK BETWEEN INFLAMMATORY SIGNALING AND METHYLATION IN CANCER. INFLAMMATION IS AN INTRICATE IMMUNE RESPONSE AGAINST INFECTION AND TISSUE DAMAGE. WHILE THE INITIAL IMMUNE RESPONSE IS IMPORTANT FOR PREVENTING TUMORIGENESIS, CHRONIC INFLAMMATION IS IMPLICATED IN CANCER PATHOGENESIS. IT HAS BEEN LINKED TO VARIOUS STAGES OF TUMOR DEVELOPMENT INCLUDING TRANSFORMATION, PROLIFERATION, ANGIOGENESIS, AND METASTASIS. IMMUNE CELLS, THROUGH THE PRODUCTION OF INFLAMMATORY MEDIATORS SUCH AS CYTOKINES, CHEMOKINES, TRANSFORMING GROWTH FACTORS, AND ADHESION MOLECULES CONTRIBUTE TO THE SURVIVAL, GROWTH, AND PROGRESSION OF THE TUMOR IN ITS MICROENVIRONMENT. THE ABERRANT EXPRESSION AND SECRETION OF PRO-INFLAMMATORY AND GROWTH FACTORS BY THE TUMOR CELLS RESULT IN THE RECRUITMENT OF IMMUNE CELLS, THUS CREATING A MUTUAL CROSSTALK. THE RECIPROCAL SIGNALING BETWEEN THE TUMOR CELLS AND THE IMMUNE CELLS CREATES AND MAINTAINS A SUCCESSFUL TUMOR NICHE. MANY INFLAMMATORY FACTORS ARE REGULATED BY EPIGENETIC MECHANISMS INCLUDING DNA METHYLATION AND HISTONE MODIFICATIONS. IN PARTICULAR, DNA AND HISTONE METHYLATION ARE CRUCIAL FORMS OF TRANSCRIPTIONAL REGULATION AND ABERRANT METHYLATION HAS BEEN ASSOCIATED WITH DEREGULATED GENE EXPRESSION IN ONCOGENESIS. SUCH DEREGULATIONS HAVE BEEN REPORTED IN BOTH SOLID TUMORS AND HEMATOLOGICAL MALIGNANCIES. WITH TECHNOLOGICAL ADVANCEMENTS TO STUDY GENOME-WIDE EPIGENETIC LANDSCAPES, IT IS NOW POSSIBLE TO IDENTIFY MOLECULAR MECHANISMS UNDERLYING ALTERED INFLAMMATORY PROFILES IN CANCER. IN THIS REVIEW, WE DISCUSS THE ROLE OF DNA AND HISTONE METHYLATION IN REGULATION OF INFLAMMATORY PATHWAYS IN HUMAN CANCERS AND REVIEW THE MERITS AND CHALLENGES OF TARGETING INFLAMMATORY MEDIATORS AS WELL AS EPIGENETIC REGULATORS IN CANCER. 2021