1 4142 119 MECHANISMS OF RESISTANCE TO TYROSINE KINASE INHIBITORS IN CHRONIC MYELOID LEUKEMIA AND RECENT THERAPEUTIC STRATEGIES TO OVERCOME RESISTANCE. GIVEN ITS RELATIVE RARITY, IT MAY AT FIRST SEEM SURPRISING THAT CHRONIC MYELOID LEUKEMIA (CML) HAS GARNERED SO MUCH ATTENTION OVER THE LAST DECADE. YET, THE ADVANCES IN MOLECULAR PATHOGENESIS THAT HAVE BEEN DERIVED FROM STUDYING THIS LEUKEMIA HAVE CLEARLY BENEFITED ALL OF ONCOLOGY. MOREOVER, THE STRIDES IN DRUG DESIGN AND DEVELOPMENT THAT HAVE ALSO ENSUED AROUND CML HAVE GIVEN RISE TO WHAT OTHERS HAVE CALLED A MOLECULAR REVOLUTION IN CANCER THERAPY. WHILE A MAJORITY OF PATIENTS WITH CHRONIC PHASE CML (CP-CML) HAVE AN EXCELLENT DURABLE RESPONSE TO IMATINIB (GLEEVEC, NOVARTIS, BASEL, SWITZERLAND), A CLEAR MINORITY WILL UNFORTUNATELY HAVE SIGNS OF PRIMARY OR SECONDARY RESISTANCE TO THERAPY. SIGNIFICANT EFFORTS GEARED TOWARD UNDERSTANDING THE MOLECULAR MECHANISMS OF IMATINIB RESISTANCE HAVE YIELDED VALUABLE INSIGHTS INTO THE BIOLOGY OF DRUG TRAFFICKING INTO AND OUT OF CELLS, EPIGENETIC CONTROL OF CELLULAR PROCESSES, ALTERATIONS IN ENZYMATIC STRUCTURES, AND THE RATIONAL STRUCTURAL-BASED DESIGN OF SMALL MOLECULE ENZYME INHIBITORS. THIS REVIEW WILL DESCRIBE THE EFFORTS AT UNDERSTANDING THE PATHOGENESIS OF IMATINIB RESISTANCE AND THE MOLECULAR RATIONALE FOR THE DEVELOPMENT OF SECOND- AND NOW THIRD-GENERATION THERAPIES FOR PATIENTS WITH CML. 2009 2 5520 27 RISK FACTORS OF POSTPARTUM DEPRESSION. POSTPARTUM DEPRESSION (PPD) IS A WIDESPREAD MENTAL HEALTH PROBLEM AND ONE OF THE PRIME CAUSES OF MATERNAL SUFFERING AND ILL HEALTH. ON A GLOBAL LEVEL, THE PREVALENCE OF THE DISORDER IS ABOUT 10 TO 15%. SYMPTOMS GENERALLY APPEAR WITHIN THE FIRST FOUR TO SIX WEEKS, WHICH IS THE HIGH-RISK PERIOD. HOWEVER, IT MAY DEVELOP UP TO ONE YEAR POST-DELIVERY. PPD PRESENTS WITH SYMPTOMS OF CLASSICAL DEPRESSION, INCLUDING MOOD FLUCTUATIONS, BOUTS OF CRYING, LACK OF INTEREST IN THE CHILD, AND EVEN THOUGHTS OF SUICIDE. PPD NOT ONLY HAS ADVERSE EFFECTS ON THE MOTHER'S HEALTH BUT ALSO HAMPERS THE GROWTH AND DEVELOPMENT OF THE CHILD. IT HAMPERS THE FORMATION OF A HEALTHY MOTHER-CHILD BOND, WHICH IN TURN MAY IMPACT FEEDING PRACTICES. THE SOCIAL ENVIRONMENT OF THE INFANT DURING THE FIRST FEW MONTHS IS PRIMARILY PROVIDED BY THE MOTHER, AND PPD MAY THUS IMPACT THE CHILD'S DEVELOPMENT. IT ALSO INCREASES THE CHILD'S SUSCEPTIBILITY TO MALNUTRITION. RESEARCH ON POSTPARTUM DEPRESSION HAS GARNERED MOMENTUM WITHIN THE LAST FEW YEARS. HOWEVER, THE MASSES ARE STILL LARGELY UNAWARE OF THE DISORDER AND ITS IMPLICATIONS. THERE IS ALSO AN INADEQUACY OF AWARENESS OF THE RISK FACTORS OF PPD. THE CROSS-CULTURAL DIFFERENCES IN MANIFESTATIONS AND APPROPRIATE PREVENTIVE MEASURES HAVE NOT BEEN EXTENSIVELY STUDIED. SOME RISK FACTORS FOR PPD ARE SIMILAR TO THOSE FOR CLASSIC DEPRESSION; HOWEVER, OBSTETRICAL AND PEDIATRIC FACTORS ARE ALSO INVOLVED. THIS LITERATURE REVIEW AIMS TO ASSESS THE CURRENTLY KNOWN RISK FACTORS FOR PPD, THEIR STRENGTH OF ASSOCIATION, AND PROBABLE MECHANISMS TO HELP IDENTIFY THE HIGH-RISK GROUP AND ENABLE THE IMPLEMENTATION OF PREVENTIVE MEASURES OR FACILITATE EARLY DIAGNOSIS. THE FACTORS IDENTIFIED SPANNED SOCIODEMOGRAPHIC, BIOLOGICAL, PSYCHOLOGICAL, AND OBSTETRIC DOMAINS. THESE INCLUDED SOCIOECONOMIC STANDING, MARITAL RELATIONSHIP, HISTORY OF PSYCHIATRIC ILLNESS, SOCIAL SUPPORT, GESTATIONAL DIABETES, VITAMIN D DEFICIENCY, IMMIGRATION STATUS, DELIVERY METHOD, VIOLENCE AND ABUSE, BIRTH EXPERIENCE, AND BIOLOGICAL AND EPIGENETIC MARKERS. THE RISK FACTORS FOR POSTPARTUM DEPRESSION ARE NUMEROUS AND MAY HAVE STRONG TO WEAK ASSOCIATIONS WITH THE DEVELOPMENT OF PPD. A PREVIOUS HISTORY OF DEPRESSION OR PSYCHIATRIC ILLNESS, DEPRESSIVE SYMPTOMS DURING PREGNANCY, GESTATIONAL DIABETES, AND A LACK OF SPOUSAL AND SOCIAL SUPPORT WERE THE MOST POWERFUL RISK FACTORS. OTHER SIGNIFICANT FACTORS INCLUDE COMPLICATIONS DURING PREGNANCY, LOW SOCIOECONOMIC STATUS, AND STRESSFUL LIFE EVENTS. STUDIES ON MATERNAL AGE AND CHRONIC ILLNESS AS RISK FACTORS WERE INCONCLUSIVE. THE ROLES OF GENETIC AND EPIGENETIC MARKERS, CULTURAL FACTORS, AND VITAMIN D INSUFFICIENCY REQUIRE FURTHER INVESTIGATION. 2022 3 4464 24 MOLECULAR MECHANISMS OF NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)/NONALCOHOLIC STEATOHEPATITIS (NASH). NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS ONE OF THE MOST COMMON CHRONIC LIVER DISEASES WORLDWIDE AND HAS GARNERED INCREASING ATTENTION IN RECENT DECADES. NAFLD IS CHARACTERIZED BY A WIDE RANGE OF LIVER CHANGES, FROM SIMPLE STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS (NASH), CIRRHOSIS, AND HEPATOCELLULAR CARCINOMA. THE PATHOGENESIS OF NAFLD/NASH IS VERY COMPLICATED AND INVOLVES LIPID ACCUMULATION, INSULIN RESISTANCE, INFLAMMATION, AND FIBROGENESIS. IN ADDITION, NAFLD IS CLOSELY ASSOCIATED WITH COMPLICATIONS SUCH AS OBESITY, DYSLIPIDEMIA, AND TYPE 2 DIABETES. IN PARTICULAR, THE CLINICAL SPECTRUM, PATHOPHYSIOLOGY, AND THERAPEUTIC OPTIONS OF NAFLD SHARE MANY THINGS IN COMMON WITH DIABETES. INSULIN RESISTANCE IS AN UNDERLYING BASIS FOR THE PATHOGENESIS OF DIABETES AND NAFLD. THIS CHAPTER FOCUSES ON THE MOLECULAR MECHANISM INVOLVED IN THE PATHOGENESIS OF INSULIN RESISTANCE, DIABETES, AND NASH/NAFLD INCLUDING THOSE THAT DRIVE DISEASE PROGRESSION SUCH AS OXIDATIVE STRESS, GENETIC AND EPIGENETIC MECHANISMS, ADIPONECTIN, CYTOKINES, AND IMMUNE CELLS. 2021 4 6566 32 TRANSLATIONAL PERSPECTIVES TO TREAT EPIDERMOLYSIS BULLOSA-WHERE DO WE STAND? EPIDERMOLYSIS BULLOSA (EB) IS THE PROTOTYPICAL EXAMPLE OF GENETIC SKIN FRAGILITY DISORDERS. GENOTYPIC HETEROGENEITY, MODIFIER GENES, EPIGENETIC, BIOCHEMICAL AND ENVIRONMENTAL FACTORS ALTER AND DETERMINE PATHOGENIC TRAITS AND, ULTIMATELY, THE WIDE AND STRIKING PHENOTYPIC VARIABILITY IN EB. BESIDES THE PRIMARY STRUCTURAL-FUNCTIONAL DEFECT, CHRONIC TISSUE DAMAGE WITH INDUCTION AND DYSREGULATION OF INFLAMMATORY PATHWAYS IS A COMMON PATHOGENIC MECHANISM IN EB. IN LOCALIZED VARIANTS, THE INFLAMMATORY ABERRATIONS MAY MAINLY AFFECT THE MICROMILIEU OF LESIONAL SKIN, WHILE A SYSTEMIC INFLAMMATORY RESPONSE WAS SHOWN TO CONTRIBUTE TO THE SYSTEMIC MORBIDITY IN SEVERE EB SUBTYPES WITH EXTENSIVE CUTANEOUS INVOLVEMENT. OUR CONTINUED UNDERSTANDING OF THE PATHOPHYSIOLOGY OF EB, AS WELL AS ADVANCES IN MOLECULAR TECHNOLOGIES, HAS PAVED THE WAY FOR TRANSLATIONAL THERAPEUTIC APPROACHES. THE SPECTRUM COMPRISES OF CORRECTIVE AND SYMPTOM-RELIEVING THERAPIES THAT INCLUDE INNOVATIVE THERAPEUTIC OPTIONS GARNERED FROM THE BENCH, REPURPOSED DRUGS APPROVED FOR OTHER DISEASES, AS WELL AS STRATEGIES FOR GENE-, PROTEIN- AND CELL-BASED THERAPIES. IMMUNOLOGICAL TRAITS FURTHER DEFINE NEW TARGETS OF THERAPY, AIMED AT IMPROVING SKIN BARRIER RESTORATION, MICROBIAL SURVEILLANCE AND INFECTION CONTROL, WOUND HEALING AND ANTI-NEOPLASTIC EFFECTS. CLINICAL AVAILABILITY AND FEASIBILITY OF THESE APPROACHES FOR ALL EB PATIENTS AND SUBTYPES ARE CURRENTLY LIMITED, REFLECTING ISSUES OF EFFICACY, SPECIFICITY, TOLERABILITY AND SAFETY. A MULTISTEP TARGETING APPROACH AND HIGHLY INDIVIDUALIZED, RISK-STRATIFIED COMBINATORY TREATMENT PLANS WILL THUS BE ESSENTIAL FOR SUSTAINED EFFICACY AND IMPROVED OVERALL QUALITY OF LIFE IN EB. 2020 5 4495 27 MORE GAIN, LESS PAIN: HOW RESISTANCE TRAINING AFFECTS IMMUNE SYSTEM FUNCTIONING IN MULTIPLE SCLEROSIS PATIENTS: A REVIEW. MULTIPLE SCLEROSIS (MS) IS CHARACTERIZED BY A COMPLEX ETIOLOGY THAT IS MIRRORED BY THE PERPLEXING AND INCONSISTENT TREATMENT RESPONSES OBSERVED ACROSS DIFFERENT PATIENTS. ALTHOUGH EPIGENETIC RESEARCH HAS GARNERED RIGHTFUL INTEREST IN ITS EFFORTS TOWARDS DEMYSTIFYING AND UNDERSTANDING ABERRANT RESPONSES TO TREATMENT, THE INTERIM UNDOUBTEDLY REQUIRES ALTERNATIVE NON-PHARMACOLOGICAL APPROACHES TOWARDS ATTAINING MORE EFFECTIVE MANAGEMENT STRATEGIES. OF PARTICULAR INTEREST IN THIS REVIEW IS RESISTANCE TRAINING (RT) AS A NON-PHARMACOLOGICAL EXERCISE-BASED INTERVENTIONAL STRATEGY AND ITS POTENTIAL ROLE AS A DISEASE-MODIFYING TOOL. RT HAS BEEN REPORTED ACROSS LITERATURE TO POSITIVELY INFLUENCE NUMEROUS ASPECTS IN THE QUALITY OF LIFE (QOL) AND FUNCTIONAL CAPACITY OF MS PATIENTS, AND ONE OF THE ATTRIBUTES OF THESE BENEFITS MAY BE A SHIFT IN THE IMMUNE SYSTEM OF THESE INDIVIDUALS. RT HAS ALSO BEEN PROVEN TO AFFECT DIFFERENT IMMUNE SYSTEM KEY PLAYERS ASSOCIATED WITH MS PATHOLOGY. ULTIMATELY, THIS BRIEF REVIEW AIMS TO PROVIDE A POTENTIAL YET CRUCIAL LINK BETWEEN RT, ALTERATIONS IN THE EXPRESSION PROFILE OF THE IMMUNE SYSTEM, AND FINALLY AN IMMINENT IMPROVEMENT IN THE OVERALL WELL-BEING AND QOL OF MS PATIENTS, SUGGESTING THAT UTILIZING RT AS AN INTERVENTIONAL EXERCISE MODALITY MAY BE AN EFFECTIVE STRATEGY THAT WOULD AID IN MANAGING SUCH A COMPLEX AND DEBILITATING DISEASE. 2023 6 2454 27 EPIGENETIC TARGETING OF HISTONE DEACETYLASES IN DIAGNOSTICS AND TREATMENT OF DEPRESSION. DEPRESSION IS A HIGHLY PREVALENT, DISABLING, AND OFTEN CHRONIC ILLNESS THAT PLACES SUBSTANTIAL BURDENS ON PATIENTS, FAMILIES, HEALTHCARE SYSTEMS, AND THE ECONOMY. A SUBSTANTIAL MINORITY OF PATIENTS ARE UNRESPONSIVE TO CURRENT THERAPIES, SO THERE IS AN URGENT NEED TO DEVELOP MORE BROADLY EFFECTIVE, ACCESSIBLE, AND TOLERABLE THERAPIES. PHARMACOLOGICAL REGULATION OF HISTONE ACETYLATION LEVEL HAS BEEN INVESTIGATED AS ONE POTENTIAL CLINICAL STRATEGY. HISTONE ACETYLATION STATUS IS CONSIDERED A POTENTIAL DIAGNOSTIC BIOMARKER FOR DEPRESSION, WHILE INHIBITORS OF HISTONE DEACETYLASES (HDACS) HAVE GARNERED INTEREST AS NOVEL THERAPEUTICS. THIS REVIEW DESCRIBES RECENT ADVANCES IN OUR KNOWLEDGE OF HISTONE ACETYLATION STATUS IN DEPRESSION AND THE THERAPEUTIC POTENTIAL OF HDAC INHIBITORS. 2021 7 6577 25 TREATMENT STRATEGIES FOR COMPLEX BEHAVIORAL INSOMNIA IN CHILDREN WITH NEURODEVELOPMENTAL DISORDERS. PURPOSE OF REVIEW: THIS REVIEW DESCRIBES RECENT RESEARCH IN PEDIATRIC BEHAVIORAL INSOMNIAS IN NEURODEVELOPMENTAL DISORDERS AND THEIR TREATMENT. RECENT FINDINGS: INSOMNIA IN CHILDREN WITH AUTISM SPECTRUM DISORDER (ASD) AND OTHER NEURODEVELOPMENTAL DISORDERS (NDDS) IS TYPICALLY COMPLEX, CHRONIC, AND DIFFICULT TO ADEQUATELY CONTROL. ABNORMALITIES IN GENETIC AND/OR EPIGENETIC REGULATION OF SLEEP/WAKEFULNESS AND ITS TIMING PREDISPOSE PATIENTS WITH NDD TO INSOMNIA, ALTHOUGH POOR SLEEP HYGIENE, MALADAPTIVE ASSOCIATIONS, AND LIMIT-SETTING ARE LIKELY TO CONTRIBUTE. PARENTS ARE AGENTS FOR CHANGE IN PROBLEMATIC SLEEP BEHAVIORS IN PATIENTS WITH NDD. WE REVIEW THE BENEFITS OF BEHAVIORAL THERAPIES AND MELATONIN TO TREAT SLEEP PROBLEMS IN CHILDREN WITH NDD. PROBLEMATIC SLEEP IS SO PREVALENT IN SOME NEURODEVELOPMENTAL SYNDROMES (RETT, ANGELMAN, WILLIAMS, AND SMITH-MAGENIS) THAT IT IS PART OF THEIR DIAGNOSTIC CRITERIA. SUMMARY: CHILDREN AND ADOLESCENTS WITH NEUROLOGICAL DISORDERS FREQUENTLY HAVE COMPLEX SLEEP DISORDERS THAT REQUIRE TREATMENT. UNDERSTANDING THE BASIC PATHOLOGY AND TREATMENT STRATEGIES PROVIDES AN OPPORTUNITY TO IMPROVE WELL BEING AND QUALITY OF LIFE IN THOSE AFFECTED BY NDD AND THEIR FAMILIES. 2013 8 1256 25 CURRENT STUDIES AND FUTURE DIRECTIONS FOR MEDULLOBLASTOMA: A REVIEW FROM THE PACIFIC PEDIATRIC NEURO-ONCOLOGY CONSORTIUM (PNOC) DISEASE WORKING GROUP. MEDULLOBLASTOMA (MB) IS THE MOST COMMON MALIGNANT CENTRAL NERVOUS SYSTEM TUMOR OF CHILDHOOD, COMPRISING A HETEROGENOUS GROUP OF TUMORS EACH WITH DISTINCT BIOLOGY, CLINICAL BEHAVIOR, AND PROGNOSIS. LONG-TERM SURVIVAL REMAINS UNACCEPTABLE, AND THOSE WHO DO SURVIVE FACE HIGH LATE MORTALITY RISK, NEW CHRONIC TREATMENT-RELATED MEDICAL CONDITIONS, NEUROCOGNITIVE IMPAIRMENTS, AND POOR HEALTH-RELATED QUALITY OF LIFE. UP-FRONT TREATMENT STRATEGIES NOW INTEGRATE MOLECULAR SUBGROUPING WITH STANDARD CLINICO-RADIOLOGICAL FACTORS TO MORE ACTUALLY RISK STRATIFY NEWLY-DIAGNOSED PATIENTS. TO WHAT EXTENT THIS NEW STRATIFICATION WILL LEAD TO IMPROVEMENTS IN TREATMENT OUTCOME WILL BE DETERMINED IN THE COMING YEARS. IN PARALLEL, DISCOVERY AND APPRECIATION FOR MEDULLOBLASTOMA'S INTER- AND INTRA-TUMORAL HETEROGENEITY CONTINUES GROWING. CLINICAL TRIALS TREATING RELAPSED DISEASE NOW ENCOMPASS PRECISION MEDICINE, EPIGENETIC MODIFICATION, AND IMMUNE THERAPY APPROACHES. THE PACIFIC PEDIATRIC NEURO-ONCOLOGY (PNOC) MEDULLOBLASTOMA WORKING GROUP IS COMMITTED TO DEVELOPING CLINICAL TRIALS BASED ON THESE EVOLVING THERAPEUTIC STRATEGIES AND SUPPORTS TRANSLATIONAL EFFORTS BY PNOC RESEARCHERS AND THE MULTI-STAKEHOLDER MEDULLOBLASTOMA COMMUNITY AT LARGE. 2023 9 5686 18 SICKLE CELL DISEASE: CLINICAL PRESENTATION AND MANAGEMENT OF A GLOBAL HEALTH CHALLENGE. SICKLE CELL DISEASE IS AN AUTOSOMAL RECESSIVE, MULTISYSTEM DISORDER, CHARACTERISED BY CHRONIC HAEMOLYTIC ANAEMIA, PAINFUL EPISODES OF VASO-OCCLUSION, PROGRESSIVE ORGAN FAILURE AND A REDUCED LIFE EXPECTANCY. SICKLE CELL DISEASE IS THE MOST COMMON MONOGENETIC DISEASE, WITH MILLIONS AFFECTED WORLDWIDE. IN WELL-RESOURCED COUNTRIES, COMPREHENSIVE CARE PROGRAMS HAVE INCREASED LIFE EXPECTANCY OF SICKLE CELL DISEASE PATIENTS, WITH ALMOST ALL INFANTS SURVIVING INTO ADULTHOOD. THERAPEUTIC OPTIONS FOR SICKLE CELL DISEASE PATIENTS ARE HOWEVER, STILL SCARCE. PREDICTORS OF SICKLE CELL DISEASE SEVERITY AND A BETTER UNDERSTANDING OF PATHOPHYSIOLOGY AND (EPI)GENETIC MODIFIERS ARE WARRANTED AND COULD LEAD TO MORE PRECISE MANAGEMENT AND TREATMENT. THIS REVIEW PROVIDES AN EXTENSIVE SUMMARY OF THE PATHOPHYSIOLOGY AND MANAGEMENT OF SICKLE CELL DISEASE AND ENCOMPASSES THE CHARACTERISTICS, COMPLICATIONS AND CURRENT AND FUTURE TREATMENT OPTIONS OF THE DISEASE. 2019 10 6048 25 THE CONCEPTS OF ASTHMA ENDOTYPES AND PHENOTYPES TO GUIDE CURRENT AND NOVEL TREATMENT STRATEGIES. ASTHMA, A COMMON, NON-COMMUNICABLE CHRONIC DISEASE AFFECTS OVER 300 MILLION INDIVIDUALS WORLDWIDE. THE WESTERN WORLD LIFESTYLE IS CLAIMED TO BE RESPONSIBLE FOR THIS HIGH AND INCREASING PREVALENCE. ASTHMA HAS BEEN DEFINED AS A SYNDROME WITH VARIOUS PHENOTYPES AND ENDOTYPES, ALLERGIC ASTHMA AND TYPE 2 ASTHMA BEING THE MOST FREQUENT. A GREAT INCREASE IN PREVALENCE OF ALLERGIC DISEASES HAS NECESSITATED INTENSIVE INVESTIGATIONS BOTH FOR UNDERSTANDING THE UNDERLYING MECHANISMS AND FOR THE DEVELOPMENT OF NOVEL THERAPY OPTIONS WITH LONG-TERM EFFICACY AND LIMITED SIDE-EFFECTS. ALLERGIC PATIENTS DEMONSTRATE UNIQUE PRESENTATIONS WITH VARIABLE VISIBLE CHARACTERISTICS AND DISEASE OUTCOMES DEPENDING ON DIFFERENT MOLECULAR MECHANISMS, RELATED TO INFLUENCE OF GENES AND EPIGENETIC CONTROL BY MICRO- AND MACRO-ENVIRONMENT. AREAS COVERED: THIS ARTICLE REVIEWS THE DEFINITION OF ASTHMA PHENOTYPES AND POSSIBLE ENDOTYPES, ADVANCES IN ALLERGY-IMMUNOLOGY FIELD AND CONTEMPORARY PERSONALIZED THERAPY OPTIONS FOR ASTHMA. EXPERT COMMENTARY: BETTER UNDERSTANDING OF THE COMPLEX IMMUNE NETWORK OF ALLERGIC INFLAMMATION AND KEY PLAYERS OF IMMUNITY IS CONTINUOUSLY BEING PROVIDED FOR CLARIFICATION OF ASTHMA SUB-TYPES. SUCCESSFUL THERAPY OF ASTHMA REQUIRES BETTER DEFINITION OF UNDERLYING PATHOGENESIS, WHICH SEQUENTIALLY COULD END UP WITH 'CUSTOM-TAILORED' INDIVIDUALIZED, EVIDENCE-BASED AND MORE PRECISE THERAPY OPTIONS; A NEW ERA TERMED AS 'PRECISION MEDICINE'. ENDOTYPE, PHENOTYPE, THERATYPE AND BIOMARKER TERMS ARISE AS MAJOR KEYWORDS IN PRECISION/PERSONALIZED MEDICINE. 2018 11 5163 29 PRECISION/PERSONALIZED MEDICINE IN ALLERGIC DISEASES AND ASTHMA. LIKE MANY OTHER CHRONIC DISEASES, EVERY ALLERGIC PATIENT HAS DIFFERENT CHARACTERISTICS BASED ON CLINICAL COURSE, TREATMENT RESPONSIVENESS AND DISEASE OUTCOMES, WHICH ARE ASSOCIATED WITH THE GENETIC AND EPIGENETIC CONTROL OF MOLECULAR MECHANISMS AND ENVIRONMENT. THIS VARIABILITY NECESSITATES THE ESTABLISHMENT OF PATIENT-TAILORED AND PRECISION APPROACHES IN HANDLING ALLERGIC DISORDERS. BETTER UNDERSTANDING OF THE UNDERLYING PATHOPHYSIOLOGICAL MECHANISMS FOR THE DEVELOPMENT OF ALLERGIC DISORDERS WILL PROVIDE MORE RATIONALE STRATEGIES BASED ON INDIVIDUAL CASES IN CONTROLLING AND TREATING THESE DISORDERS. ENDOTYPING, PHENOTYPING, GENOTYPING AND THERATYPING, AND BIOMARKERS ARE KEYWORDS IN THIS AREA AND HAVE BEEN GAINING LOTS OF ATTENTION IN THE FIELD OF PRECISION MEDICINE, WHICH AIMS TO REVOLUTIONIZE PATIENT CARE AND DEVELOP BETTER PREVENTION AND TREATMENT STRATEGIES. IN ADDITION, PRECISION HEALTH IS A NEW CONCEPT THAT BRINGS PRECISE APPROACHES TO THE SCENE FOR BEING HEALTHY AND PREVENTION OF ALLERGIC DISEASE AND ASTHMA. THE SPECIALTY OF ALLERGY HAS A LEADING ROLE IN THE FIELD, BECAUSE ALLERGEN-SPECIFIC IMMUNOTHERAPY STARTED 105 YEARS AGO, AND IS HISTORICALLY A LEADING PERSONALIZED/PRECISION MEDICINE APPROACH IN ALL MEDICINE DISCIPLINES PROVIDING THE POSSIBILITY OF CURE IN AN INDIVIDUALIZED MANNER INSTEAD OF CONVENTIONAL SYMPTOMATIC TREATMENTS. 2018 12 3606 23 IMPROVING TREATMENT OF NEURODEVELOPMENTAL DISORDERS: RECOMMENDATIONS BASED ON PRECLINICAL STUDIES. INTRODUCTION: NEURODEVELOPMENTAL DISORDERS (NDDS) ARE COMMON AND SEVERELY DEBILITATING. THEIR CHRONIC NATURE AND RELIANCE ON BOTH GENETIC AND ENVIRONMENTAL FACTORS MAKES STUDYING NDDS AND THEIR TREATMENT A CHALLENGING TASK. AREAS COVERED: HEREIN, THE AUTHORS DISCUSS THE NEUROBIOLOGICAL MECHANISMS OF NDDS, AND PRESENT RECOMMENDATIONS ON THEIR TRANSLATIONAL RESEARCH AND THERAPY, OUTLINED BY THE INTERNATIONAL STRESS AND BEHAVIOR SOCIETY. VARIOUS DRUGS CURRENTLY PRESCRIBED TO TREAT NDDS ALSO REPRESENT A HIGHLY DIVERSE GROUP. ACTING ON VARIOUS NEUROTRANSMITTER AND PHYSIOLOGICAL SYSTEMS, THESE DRUGS OFTEN LACK SPECIFICITY OF ACTION, AND ARE COMMONLY USED TO TREAT MULTIPLE OTHER PSYCHIATRIC CONDITIONS. THERE HAS ALSO BEEN RELATIVELY LITTLE PROGRESS IN THE DEVELOPMENT OF NOVEL MEDICATIONS TO TREAT NDDS. BASED ON CLINICAL, PRECLINICAL AND TRANSLATIONAL MODELS OF NDDS, OUR RECOMMENDATIONS COVER A WIDE RANGE OF METHODOLOGICAL APPROACHES AND CONCEPTUAL STRATEGIES. EXPERT OPINION: TO IMPROVE PHARMACOTHERAPY AND DRUG DISCOVERY FOR NDDS, WE NEED A STRONGER EMPHASIS ON TARGETING MULTIPLE ENDOPHENOTYPES, A BETTER DISSECTION OF GENETIC/EPIGENETIC FACTORS OR "HIDDEN HERITABILITY," AND A CAREFUL CONSIDERATION OF POTENTIAL DEVELOPMENTAL/TROPHIC ROLES OF BRAIN NEUROTRANSMITTERS. THE VALIDITY OF ANIMAL NDD MODELS CAN BE IMPROVED THROUGH DISCOVERY OF NOVEL (BEHAVIORAL, PHYSIOLOGICAL AND NEUROIMAGING) BIOMARKERS, APPLYING PROPER ENVIRONMENTAL ENRICHMENT, WIDENING THE SPECTRUM OF MODEL ORGANISMS, TARGETING DEVELOPMENTAL TRAJECTORIES OF NDD-RELATED BEHAVIORS AND COMORBID CONDITIONS BEYOND TRADITIONAL NDDS. WHILE THESE RECOMMENDATIONS CANNOT BE ADDRESSED ALL IN ONCE, OUR INCREASED UNDERSTANDING OF NDD PATHOBIOLOGY MAY TRIGGER INNOVATIVE CROSS-DISCIPLINARY RESEARCH EXPANDING BEYOND TRADITIONAL METHODS AND CONCEPTS. 2016 13 5161 32 PRECISION AND PERSONALIZED MEDICINE: HOW GENOMIC APPROACH IMPROVES THE MANAGEMENT OF CARDIOVASCULAR AND NEURODEGENERATIVE DISEASE. LIFE EXPECTANCY HAS GRADUALLY GROWN OVER THE LAST CENTURY. THIS HAS DEEPLY AFFECTED HEALTHCARE COSTS, SINCE THE GROWTH OF AN AGING POPULATION IS CORRELATED TO THE INCREASING BURDEN OF CHRONIC DISEASES. THIS REPRESENTS THE INTERESTING CHALLENGE OF HOW TO MANAGE PATIENTS WITH CHRONIC DISEASES IN ORDER TO IMPROVE HEALTH CARE BUDGETS. EFFECTIVE PRIMARY PREVENTION COULD REPRESENT A PROMISING ROUTE. TO THIS END, PRECISION, TOGETHER WITH PERSONALIZED MEDICINE, ARE USEFUL INSTRUMENTS IN ORDER TO INVESTIGATE PATHOLOGICAL PROCESSES BEFORE THE APPEARANCE OF CLINICAL SYMPTOMS AND TO GUIDE PHYSICIANS TO CHOOSE A TARGETED THERAPY TO MANAGE THE PATIENT. CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES REPRESENT SUITABLE MODELS FOR TAKING FULL ADVANTAGE OF PRECISION MEDICINE TECHNOLOGIES APPLIED TO ALL STAGES OF DISEASE DEVELOPMENT. THE AVAILABILITY OF HIGH TECHNOLOGY INCORPORATING ARTIFICIAL INTELLIGENCE AND ADVANCEMENT PROGRESS MADE IN THE FIELD OF BIOMEDICAL RESEARCH HAVE BEEN SUBSTANTIAL TO UNDERSTAND HOW GENES, EPIGENETIC MODIFICATIONS, AGING, NUTRITION, DRUGS, MICROBIOME AND OTHER ENVIRONMENTAL FACTORS CAN IMPACT HEALTH AND CHRONIC DISORDERS. THE AIM OF THE PRESENT REVIEW IS TO ADDRESS HOW PRECISION AND PERSONALIZED MEDICINE CAN BRING GREATER CLARITY TO THE CLINICAL AND BIOLOGICAL COMPLEXITY OF THESE TYPES OF DISORDERS ASSOCIATED WITH HIGH MORTALITY, INVOLVING TREMENDOUS HEALTH CARE COSTS, BY DESCRIBING IN DETAIL THE METHODS THAT CAN BE APPLIED. THIS MIGHT OFFER PRECIOUS TOOLS FOR PREVENTIVE STRATEGIES AND POSSIBLE CLUES ON THE EVOLUTION OF THE DISEASE AND COULD HELP IN PREDICTING MORBIDITY, MORTALITY AND DETECTING CHRONIC DISEASE INDICATORS MUCH EARLIER IN THE DISEASE COURSE. THIS, OF COURSE, WILL HAVE A MAJOR EFFECT ON BOTH IMPROVING THE QUALITY OF CARE AND QUALITY OF LIFE OF THE PATIENTS AND REDUCING TIME EFFORTS AND HEALTHCARE COSTS. 2020 14 958 24 CHRONIC MYELOMONOCYTIC LEUKEMIA - A REVIEW. INTRODUCTION: CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML) IS A CLONAL MYELOID NEOPLASM, DENOTED BY OVERLAPPING MYELODYSPLASTIC AND MYELOPROLIFERATIVE FEATURES, WITH POOR OVERALL SURVIVAL AND HIGH TRANSFORMATION RATE TO ACUTE MYELOID LEUKEMIA. AREAS COVERED: THIS REVIEW, FOLLOWING A THOROUGH MEDLINE SEARCH OF PERTINENT PUBLISHED LITERATURE, DISCUSSES THE DIAGNOSTIC CRITERIA, THE PATHOGENESIS, AND THE COMPLEX GENETIC LANDSCAPE OF THE DISEASE. PROGNOSTICATION, RESPONSE CRITERIA, THERAPEUTIC MANAGEMENT OF PATIENTS, EFFICACY OF ESTABLISHED AND NOVEL TREATMENT MODALITIES ARE THOROUGHLY REVIEWED. EXPERT OPINION: CYTOGENETIC ABNORMALITIES AND MUTATIONS IN GENES INVOLVED IN EPIGENETIC AND TRANSCRIPTIONAL REGULATION, AND CELL-SIGNALING ARE ABUNDANT IN CMML AND IMPLICATED IN ITS COMPLEX PATHOGENESIS. AS PRESENCE OF THESE MUTATIONS CARRY A PROGNOSTIC IMPACT, THEY ARE INCREASINGLY INCORPORATED IN RISK-STRATIFICATION SCHEMES. NOVEL RESPONSE CRITERIA HAVE BEEN PROPOSED, CONSIDERING THE UNIQUE FEATURES OF THE DISEASE. ALTHOUGH ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION REMAINS THE ONLY TREATMENT WITH CURATIVE INTENT, IT IS RESERVED FOR A MINORITY OF PATIENTS; THEREFORE, THERE IS AN UNMET NEED FOR OPTIMIZING TREATMENT MODALITIES, SUCH AS HYPOMETHYLATING AGENTS, AND INTRODUCING NOVEL AGENTS, WHICH COULD SUBSTANTIALLY IMPROVE SURVIVAL AND QUALITY OF LIFE OF CMML PATIENTS. CLINICAL TRIALS DEDICATED SPECIFICALLY TO CMML ARE NEEDED TO EXPLORE THE EFFICACY AND SAFETY OF NOVEL TREATMENT MODALITIES. 2021 15 6480 24 TOWARDS PRECISION MEDICINE IN GENERALIZED ANXIETY DISORDER: REVIEW OF GENETICS AND PHARMACO(EPI)GENETICS. GENERALIZED ANXIETY DISORDER (GAD) IS A PREVALENT AND CHRONIC MENTAL DISORDER THAT ELICITS WIDESPREAD FUNCTIONAL IMPAIRMENT. GIVEN THE HIGH DEGREE OF NON-RESPONSE/PARTIAL RESPONSE AMONG PATIENTS WITH GAD TO AVAILABLE PHARMACOLOGICAL TREATMENTS, THERE IS A STRONG NEED FOR NOVEL APPROACHES THAT CAN OPTIMIZE OUTCOMES, AND LEAD TO MEDICATIONS THAT ARE SAFER AND MORE EFFECTIVE. ALTHOUGH INVESTIGATIONS HAVE IDENTIFIED INTERESTING TARGETS PREDICTING TREATMENT RESPONSE THROUGH PHARMACOGENETICS (PGX), PHARMACO-EPIGENETICS, AND NEUROIMAGING METHODS, THESE STUDIES ARE OFTEN SOLITARY, NOT REPLICATED, AND CARRY SEVERAL LIMITATIONS. THIS REVIEW PROVIDES AN OVERVIEW OF THE CURRENT STATUS OF GAD GENETICS AND PGX AND PRESENTS POTENTIAL STRATEGIES TO IMPROVE TREATMENT RESPONSE BY COMBINING BETTER PHENOTYPING WITH PGX AND IMPROVED ANALYTICAL METHODS. THESE STRATEGIES CARRY THE DUAL BENEFIT OF DELIVERING DATA ON BIOMARKERS OF TREATMENT RESPONSE AS WELL AS POINTING TO DISEASE MECHANISMS THROUGH THE BIOLOGY OF THE MARKERS ASSOCIATED WITH RESPONSE. OVERALL, THESE EFFORTS CAN SERVE TO IDENTIFY CLINICAL, GENETIC, AND EPIGENETIC FACTORS THAT CAN BE INCORPORATED INTO A PHARMACO(EPI)GENETIC TEST THAT MAY ULTIMATELY IMPROVE TREATMENT RESPONSE AND REDUCE THE SOCIOECONOMIC BURDEN OF GAD. 2019 16 4884 24 OVERVIEW OF THE PATHOGENESIS, GENETIC, AND NON-INVASIVE CLINICAL, BIOCHEMICAL, AND SCORING METHODS IN THE ASSESSMENT OF NAFLD. NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS THE MOST PREVALENT CHRONIC LIVER DISEASE WORLDWIDE. IT REPRESENTS A RANGE OF DISORDERS, INCLUDING SIMPLE STEATOSIS, NONALCOHOLIC STEATOHEPATITIS (NASH), AND LIVER CIRRHOSIS, AND ITS PREVALENCE CONTINUES TO RISE. IN SOME CASES, HEPATOCELLULAR CARCINOMA (HCC) MAY DEVELOP. THE DEVELOP;MENT OF NON-INVASIVE DIAGNOSTIC AND SCREENING TOOLS IS NEEDED, IN ORDER TO REDUCE THE FREQUENCY OF LIVER BIOPSIES. THE MOST PROMISING METHODS ARE THOSE ABLE TO EXCLUDE ADVANCED FIBROSIS AND QUANTIFY STEATOSIS. IN THIS STUDY, NEW PERSPECTIVE MARKERS FOR INFLAMMATION, OXIDATIVE STRESS, APOPTOSIS, AND FIBROGENESIS; EMERGING SCORING MODELS FOR DETECTING HEPATIC STEATOSIS AND FIBROSIS; AND NEW GENETIC, EPIGENETIC, AND MULTIOMIC STUDIES ARE DISCUSSED. AS ISOLATED BIOCHEMICAL PARAMETERS ARE NOT SPECIFIC OR SENSITIVE ENOUGH TO PREDICT THE PRESENCE OF NASH AND FIBROSIS, THERE IS A TENDENCY TO USE VARIOUS MARKERS AND COMBINE THEM INTO MATHEMATICAL ALGORITHMS. SEVERAL PREDICTIVE MODELS AND SCORING SYSTEMS HAVE BEEN DEVELOPED. CURRENT DATA SUGGESTS THAT PANELS OF MARKERS (NAFLD FIBROSIS SCORE, FIB-4 SCORE, BARD SCORE, AND OTHERS) ARE USEFUL DIAGNOSTIC MODALITIES TO MINIMIZE THE NUMBER OF LIVER BIOPSIES. THE REVIEW UNVEILS PATHOPHYSIOLOGICAL ASPECTS RELATED TO NEW TRENDS IN CURRENT NON-INVASIVE BIOCHEMICAL, GENETIC, AND SCORING METHODS, AND PROVIDES INSIGHT INTO THEIR DIAGNOSTIC ACCURACIES AND SUITABILITY IN CLINICAL PRACTICE. 2019 17 264 28 ADVANCING ASTHMA CARE: THE GLASS IS ONLY HALF FULL! OVER THE PAST 20 YEARS, THERE HAS BEEN A CONCERTED EFFORT IN THE UNITED STATES TO REDUCE MORBIDITY RELATED TO CHRONIC DISEASE, INCLUDING ASTHMA. ATTENTION WAS INITIALLY DIRECTED TOWARD ASTHMA IN RESPONSE TO THE RECOGNITION THAT ASTHMA MORTALITY WAS INCREASING AND THAT THE BURDEN OF DISEASE WAS SIGNIFICANT. THESE EFFORTS TO ADDRESS ASTHMA MORTALITY LED TO MANY NEW INITIATIVES TO DEVELOP CLINICAL PRACTICE GUIDELINES, IMPLEMENT THE ASTHMA GUIDELINES INTO CLINICAL PRACTICE, CONDUCT RESEARCH TO FILL THE GAPS IN THE GUIDELINES, AND CONTINUOUSLY REVISE THE ASTHMA GUIDELINES AS MORE INFORMATION BECAME AVAILABLE. AN ASSESSMENT OF OUR PROGRESS SHOWS SIGNIFICANT ACCOMPLISHMENTS IN RELATION TO REDUCING ASTHMA MORTALITY AND HOSPITALIZATIONS. CONSEQUENTLY, WE ARE NOW AT A CROSSROADS IN ASTHMA CARE. ALTHOUGH WE HAVE RECOGNIZED SOME REMARKABLE ACCOMPLISHMENTS IN REDUCING ASTHMA MORTALITY AND MORBIDITY, THE AVAILABILITY OF NEW TOOLS TO MONITOR DISEASE ACTIVITY, INCLUDING BIOMARKERS AND EPIGENETIC MARKERS, ALONG WITH INFORMATION TECHNOLOGY SYSTEMS TO MONITOR ASTHMA CONTROL HOLD SOME PROMISE IN IDENTIFYING GAPS IN DISEASE MANAGEMENT. THESE ADVANCES SHOULD PROMPT THE EVOLUTION OF NEW STRATEGIES AND NEW TREATMENTS TO FURTHER REDUCE DISEASE BURDEN. IT NOW BECOMES IMPERATIVE TO CONTINUE A FOCUS ON WAYS TO FURTHER REDUCE THE BURDEN OF ASTHMA AND PREVENT ITS ONSET. 2011 18 3022 26 GENETICS AND EPIGENETICS PURPOSE IN NONALCOHOLIC FATTY LIVER DISEASE. INTRODUCTION: NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) COMPRISES A BROAD SPECTRUM OF DISEASES, WHICH CAN PROGRESS FROM BENIGN STEATOSIS TO NONALCOHOLIC STEATOHEPATITIS, LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA. NAFLD IS THE MOST COMMON CHRONIC LIVER DISEASE IN DEVELOPED COUNTRIES, AFFECTING APPROXIMATELY 25% OF THE GENERAL POPULATION. INSULIN RESISTANCE, ADIPOSE TISSUE DYSFUNCTION, MITOCHONDRIAL AND ENDOPLASMIC RETICULUM STRESS, CHRONIC INFLAMMATION, GENETIC AND EPIGENETIC FACTORS ARE NAFLD TRIGGERS THAT CONTROL THE DISEASE SUSCEPTIBILITY AND PROGRESSION. AREAS COVERED: IN RECENT YEARS A LARGE NUMBER OF INVESTIGATIONS HAVE BEEN CARRIED OUT TO ELUCIDATE GENETIC AND EPIGENETIC FACTORS IN THE DISEASE PATHOGENESIS, AS WELL AS THE SEARCH FOR DIAGNOSTIC MARKERS AND THERAPEUTIC TARGETS. THIS PAPER OBJECTIVE IS TO REPORT THE MOST STUDIED GENETIC AND EPIGENETIC VARIANTS AROUND NAFLD. EXPERT OPINION: NAFLD LEAD TO VARIOUS COMORBIDITIES, WHICH HAVE A CONSIDERABLE IMPACT ON THE PATIENT WELLNESS AND LIFE QUALITY, AS WELL AS ON THE COSTS THEY GENERATE FOR THE COUNTRY'S HEALTH SERVICES. IT IS ESSENTIAL TO CONTINUE WITH MOLECULAR RESEARCH, SINCE IT COULD BE USED AS A CLINICAL TOOL FOR PROGNOSIS AND DISEASE SEVERITY. SPECIFICALLY, IN THE FIELD OF HEPATOLOGY, PLASMA MIRNAS COULD PROVIDE A NOVEL TOOL IN LIVER DISEASES DIAGNOSIS AND MONITORING, REPRESENTING AN ALTERNATIVE TO INVASIVE DIAGNOSTIC PROCEDURES. 2020 19 4712 20 NON-ALCOHOLIC FATTY LIVER DISEASE: METABOLIC, GENETIC, EPIGENETIC AND ENVIRONMENTAL RISK FACTORS. NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS ONE OF THE MOST FREQUENT CAUSES OF CHRONIC LIVER DISEASE IN THE WESTERN WORLD, PROBABLY DUE TO THE GROWING PREVALENCE OF OBESITY, METABOLIC DISEASES, AND EXPOSURE TO SOME ENVIRONMENTAL AGENTS. IN CERTAIN PATIENTS, SIMPLE HEPATIC STEATOSIS CAN PROGRESS TO NON-ALCOHOLIC STEATOHEPATITIS (NASH), WHICH CAN SOMETIMES LEAD TO LIVER CIRRHOSIS AND ITS COMPLICATIONS INCLUDING HEPATOCELLULAR CARCINOMA. UNDERSTANDING THE MECHANISMS THAT CAUSE THE PROGRESSION OF NAFLD TO NASH IS CRUCIAL TO BE ABLE TO CONTROL THE ADVANCEMENT OF THE DISEASE. THE MAIN HYPOTHESIS CONSIDERS THAT IT IS DUE TO MULTIPLE FACTORS THAT ACT TOGETHER ON GENETICALLY PREDISPOSED SUBJECTS TO SUFFER FROM NAFLD INCLUDING INSULIN RESISTANCE, NUTRITIONAL FACTORS, GUT MICROBIOTA, AND GENETIC AND EPIGENETIC FACTORS. IN THIS ARTICLE, WE WILL DISCUSS THE EPIDEMIOLOGY OF NAFLD, AND WE OVERVIEW SEVERAL TOPICS THAT INFLUENCE THE DEVELOPMENT OF THE DISEASE FROM SIMPLE STEATOSIS TO LIVER CIRRHOSIS AND ITS POSSIBLE COMPLICATIONS. 2021 20 734 28 CANCER HEALTHCARE DISPARITIES AMONG AFRICAN AMERICANS IN THE UNITED STATES. A NEED EXISTS TO EXAMINE RACIAL DISPARITIES IN THE HEALTHCARE ARENA AND THE IMPACT ON PATIENTS WITH CANCER. DESPITE ONGOING EFFORTS TO INCREASE EQUITY IN PRIMARY HEALTHCARE ACCESS, RACIAL AND SOCIOECONOMIC DISPARITIES PERSIST, THUS CONTRIBUTING TO DISPROPORTIONATE TREATMENT OUTCOMES AND SURVIVORSHIP AMONG MINORITY AND LOW-INCOME PATIENTS. SUCH DISPARITIES HAVE BEEN REVEALED IN TREATMENT COHORTS OF PATIENTS WITH MULTIPLE FORMS OF CANCER, INCLUDING BREAST, CERVICAL, OVARIAN, ENDOMETRIAL, PROSTATE, LUNG, COLORECTAL, GASTROINTESTINAL, AND HEPATOCELLULAR, AND HAVE BEEN ATTRIBUTED TO A RANGE OF CO-OCCURRING BEHAVIORAL, SOCIAL DETERMINANTS OF HEALTH, UNDERLYING GENETIC FACTORS, AS WELL AS ACCESS TO EDUCATIONAL OPPORTUNITIES THAT LIMIT THE QUALITY OF INFORMED HEALTHCARE. THESE VARIOUS INTERRELATED FACTORS WIDEN CANCER HEALTHCARE DISPARITIES SYNERGISTICALLY THROUGHOUT UNDERSERVED COMMUNITIES, AND THEIR INFLUENCE HAS BEEN AMPLIFIED BY THE CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC. FUNDAMENTALLY, A LACK OF BASIC AND CLINICAL RESEARCH EXISTS THAT FAILS TO ADEQUATELY REFLECT DIVERSITY AND MINORITY INVOLVEMENT IN DRUG DEVELOPMENT. ALTHOUGH OVERCOMING THE OBSTACLES RESPONSIBLE FOR CHRONIC TREATMENT DISPARITIES IS A FORMIDABLE TASK, PROMISING MEANS OF ACHIEVING MORE UNIFORM QUALITY HEALTHCARE ARE BECOMING MORE CLEARLY ELUCIDATED. TO REDUCE DISEASE PROGRESSION, INCREASE OVERALL SURVIVAL, AND IMPROVE THE HEALTH OF VULNERABLE POPULATIONS, IT IS NECESSARY TO IDENTIFY AND FULLY DISCLOSE ENVIRONMENTAL, BIOLOGICAL, AND ANCESTRAL FACTORS THAT IMPACT THE RISK FOR CANCER; HEAL HISTORICAL FRACTURES WITHIN COMMUNITIES; AND INCREASE PARTICIPATION OF RACIAL AND ETHNIC MINORITIES IN SCREENING EFFORTS AND RESEARCH STUDIES. THIS REQUIRES DEVELOPING A SYSTEM OF JUSTICE AND TRUST BASED ON SPECIFIC, SOLUTION-ORIENTED GRASSROOTS COMMUNITY EFFORTS WORKING IN TANDEM WITH MEDICAL AND PHARMACEUTICAL LEADERS. BY FULLY EXPLORING AND PINPOINTING THE UNDERLYING CAUSES OF HEALTHCARE DISPARITIES, IT SHOULD BE POSSIBLE TO DEFINE STRATEGIES AND INTERVENTIONS MOST LIKELY TO TRANSFORM CANCER CARE. THE ULTIMATE GOAL IS UNDERSTANDING INDIVIDUAL, CULTURAL, AND BIOLOGICAL VULNERABILITIES, INCLUDING ENVIRONMENTAL AND EPIGENETIC LIABILITIES, TO OPTIMIZE CANCER PREVENTION, DIAGNOSIS, AND TREATMENT. 2022