PLoS Genet. 2021 Aug 30;17(8):e1009713. doi: 10.1371/journal.pgen.1009713. Online ahead of print.

ABSTRACT

Genome-wide association studies (GWASs) have uncovered a wealth of associations between common variants and human phenotypes. Here, we present an integrative analysis of GWAS summary statistics from 36 phenotypes to decipher multitrait genetic architecture and its link with biological mechanisms. Our framework incorporates multitrait association mapping along with an investigation of the breakdown of genetic associations into clusters of variants harboring similar multitrait association profiles. Focusing on two subsets of immunity and metabolism phenotypes, we then demonstrate how genetic variants within clusters can be mapped to biological pathways and disease mechanisms. Finally, for the metabolism set, we investigate the link between gene cluster assignment and the success of drug targets in randomized controlled trials.

PMID:34460823 | DOI:10.1371/journal.pgen.1009713

JAMA Neurol. 2021 Aug 30. doi: 10.1001/jamaneurol.2021.2598. Online ahead of print.

ABSTRACT

IMPORTANCE: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.

OBJECTIVE: To identify the genetic variants associated with juvenile ALS.

DESIGN, SETTING, AND PARTICIPANTS: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.

MAIN OUTCOMES AND MEASURES: De novo variants present only in the index case and not in unaffected family members.

RESULTS: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.

CONCLUSIONS AND RELEVANCE: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.

PMID:34459874 | DOI:10.1001/jamaneurol.2021.2598

Br J Dermatol. 2021 Aug 30. doi: 10.1111/bjd.20693. Online ahead of print.

NO ABSTRACT

PMID:34459498 | DOI:10.1111/bjd.20693

JAMIA Open. 2021 Aug 27;4(3):ooab067. doi: 10.1093/jamiaopen/ooab067. eCollection 2021 Jul.

ABSTRACT

BACKGROUND: Applied pharmacogenomics presents opportunities for improving patient care through precision medicine, particularly when paired with appropriate clinical decision support (CDS). However, a lack of patient resources for understanding pharmacogenomic test results may hinder shared decision-making and patient confidence in treatment. We sought to create a patient pharmacogenomics education and results delivery platform complementary to a CDS system to facilitate further research on the relevance of patient education to pharmacogenomics.

METHODS: We conceptualized a model that extended the data access layer of an existing institutional CDS tool to allow for the pairing of decision supports offered to providers with patient-oriented summaries at the same level of phenotypic specificity. We built a two-part system consisting of a secure portal for patient use and an administrative dashboard for patient summary creation. The system was built in an ASP.NET and AngularJS architecture, and all data was housed in a HIPAA-compliant data center, with PHI secure in transit and at rest.

RESULTS: The YourPGx Patient Portal was deployed on the institutional network in June 2019. Fifty-eight unique patient portal summaries have been written so far, which can provide over 4500 results modules to the pilot population of 544 patients. Patient behavior on the portal is being logged for further research.

CONCLUSIONS: To our knowledge, this is the first automated system designed and deployed to provide detailed, personalized patient pharmacogenomics education complementary to a clinical decision support system. Future work will expand upon this system to allow for telemedicine and patient notification of new or updated results.

PMID:34458686 | PMC:PMC8390782 | DOI:10.1093/jamiaopen/ooab067

Biol Psychiatry. 2021 Jul 7:S0006-3223(21)01429-3. doi: 10.1016/j.biopsych.2021.06.021. Online ahead of print.

ABSTRACT

BACKGROUND: Alterations in the immune system, particularly C4A, have been implicated in the pathophysiology of schizophrenia. C4A promotes synapse elimination by microglia in preclinical models; however, it is unknown whether this process is also present in living humans and how it affects brain morphology.

METHODS: Participants (N = 111; 33 patients with psychosis, 37 individuals at clinical high risk, and 41 healthy control subjects) underwent a TSPO [18F]FEPPA positron emission tomography scan and a magnetic resonance imaging scan. Brain C4A expression was genetically predicted as a function of the dosage of each of 4 structural elements (C4AL, C4BL, C4AS, C4BS).

RESULTS: Higher genetically predicted brain C4A expression was associated with higher brain microglial marker (TSPO) and altered hippocampal morphology, including reduced surface area and medial displacement in the CA1 area. This study is the first to quantify genetically predicted brain C4A expression in individuals at clinical high risk, showing significantly lower C4A in individuals at clinical high risk compared with healthy control subjects. We also showed a robust effect of sex on genetically predicted brain C4A expression and effects of both sex and cannabis use on brain TSPO.

CONCLUSIONS: This study shows for the first time complement system (C4A) coupling with a microglial marker (TSPO) and hippocampal morphology in living human brain. These findings pave the way for future research on the interaction between C4A and glial cell function, which has the potential to inform the disease mechanism underlying psychosis and schizophrenia.

PMID:34456009 | DOI:10.1016/j.biopsych.2021.06.021

Eur J Pharmacol. 2021 Aug 25:174444. doi: 10.1016/j.ejphar.2021.174444. Online ahead of print.

ABSTRACT

Pyroptosis is mainly considered a gasdermin-regulated cell death mechanism characterized by cellular lysis and the release of several pro-inflammatory factors. Nowadays, pyroptosis has notably been gained extensive attention from clinicians and researchers. However, current studies report that downregulation of pyroptosis-mediated cell death plays a significant role in developing multiple cancers. Increasing studies also suggest that pyroptosis can impact all stages of carcinogenesis. Inducing pyroptotic cellular death could be a promising therapeutic option for managing and regulating multiple cancers in the near future. Our current review highlights the molecular and morphological features of pyroptosis and its potential roles in various cancers. In addition, we have also highlighted the biological characteristics and significances of GSDMD and GSDME and their critical functions in cancer progression, management, and regulation.

PMID:34453928 | DOI:10.1016/j.ejphar.2021.174444

Eur J Clin Pharmacol. 2021 Aug 28. doi: 10.1007/s00228-021-03146-5. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this paper is to study the correlation between demographic and clinical factors and warfarin dose of patients in Chinese Han population taking warfarin and study gene polymorphisms impact of related gene loci (CYP2C9*3, VKORC1-1639G > A) on warfarin doses, to establish a model to predict initial standard dose and maintenance dose based on CYP2C9*3, VKORC1-1639G > A genotype.

METHODS: The study collects the data of patients in our hospital and other subcenters which incorporates 2160 patients to establish the initial dose model and 1698 patients for the stable dose model, and sequences 26 multigene sites in 451 patients. Based on the patient's dosage, clinical data, and demographic characteristics, the genetic and non-genetic effects on the initial dose and stable dose of warfarin are calculated by using statistical methods, and the prediction model of initial standard dose and maintenance dose can be established via multiple linear regression.

RESULTS: The initial dose of warfarin (mg/day) was calculated as (1.346 + 0.350 × (VKORC1-1639G > A) - 0.273 × (CYP2C9*3) + 0.245 × (body surface area) - 0.003 × (age) - 0.036 × (amine-iodine) + 0.021 × (sex))2. This model incorporated seven factors and explained 55.3% of the individualization differences of the warfarin drug dose. The maintenance dose of warfarin (mg/day) was calculated as (1.336 + 0.299 × (VKORC1-1639G > A) + 0.480 × (body surface area) - 0.214 × (CYP2C9*3) - 0.074 × (amine-iodine) - 0.003 × (age) - 0.077 × (statins) - 0.002 × (height))2. This model incorporated six factors and explained 42.4% of the individualization differences in the warfarin drug dose.

CONCLUSION: The genetic and non-genetic factors affecting warfarin dose in Chinese Han population were studied systematically in this study. The pharmacogenomic dose prediction model constructed in this study can predict anticoagulant efficacy of warfarin and has potential application value in clinical practice.

PMID:34453556 | DOI:10.1007/s00228-021-03146-5

Clin Pharmacol Ther. 2021 Aug 28. doi: 10.1002/cpt.2404. Online ahead of print.

ABSTRACT

Atovaquone-proguanil (ATV-PG) plus amodiaquine (AQ) has been considered as a potential replacement for sulfadoxine-pyrimethamine plus AQ for seasonal malaria chemoprevention (SMC) in African children. This randomized, double-blind, placebo-controlled, parallel group study assessed the safety, tolerability, and pharmacokinetics (PK) of ATV-PG plus AQ in healthy adult males and females of Black sub-Saharan African origin. Participants were randomized to four treatment groups: ATV-PG/AQ (n=8), ATV-PG/placebo (n=12), AQ/placebo (n=12), and placebo/placebo (n=12). Treatments were administered orally once daily for three days (Days 1-3) at daily doses of ATV-PQ 1000/400 mg and AQ 612 mg. Co-administration of ATV-PG/AQ had no clinically relevant effect on PK parameters for ATV, PG, the PG metabolite cycloguanil, AQ or the AQ metabolite N-desethyl-amodiaquine. Adverse events occurred in 8/8 (100%) of participants receiving ATV-PG/AQ, 11/12 (91.7%) receiving ATV-PG, 11/12 (91.7%) receiving AQ, and 3/12 (25%) receiving placebo. The safety and tolerability profiles of ATV-PG and AQ were consistent with previous reports. In the ATV-PG/AQ group, 2/8 participants experienced extrapyramidal adverse effects (EPAE) on Day 3, both psychiatric and physical, which appeared unrelated to drug plasma PK or cytochrome P450 2C8 phenotype. Although rare cases are reported with AQ administration, the high incidence of EPAE was unexpected in this small study. Owing to the unanticipated increased frequency of EPAE observed, the combination of ATV-PQ plus AQ is not recommended for further evaluation in prophylaxis of malaria in African children.

PMID:34453327 | DOI:10.1002/cpt.2404

Mol Psychiatry. 2021 Aug 27. doi: 10.1038/s41380-021-01256-1. Online ahead of print.

ABSTRACT

Drug addiction, one of the major health problems worldwide, is characterized by the loss of control in drug intake, craving, and withdrawal. At the individual level, drugs of abuse produce serious consequences on health and have a negative impact on the family environment and on interpersonal and work relationships. At a wider scale, they have significant socio-economic and public health consequences and they cause delinquency and citizen insecurity. Cocaine, a psychostimulant substance, is one of the most used illicit drugs, especially in America, Western Europe, and Australia. Cocaine use disorders (CUD) are complex multifactorial conditions driven by both genetic and environmental influences. Importantly, not all people who use cocaine develop CUD, and this is due, at least in part, to biological factors that are encoded in the genome of individuals. Acute and repeated use of cocaine induces epigenetic and gene expression changes responsible for the neuronal adaptations and the remodeling of brain circuits that lead to the transition from use to abuse or dependence. The purpose of this review is to delineate such factors, which should eventually help to understand the inter-individual variability in the susceptibility to cocaine addiction. Heritability estimates for CUD are high and genetic risk factors for cocaine addiction have been investigated by candidate gene association studies (CGAS) and genome-wide association studies (GWAS), reviewed here. Also, the high comorbidity that exists between CUD and several other psychiatric disorders is well known and includes phenotypes like schizophrenia, aggression, antisocial or risk-taking behaviors. Such comorbidities are associated with a worse lifetime trajectory, and here we report shared genetic factors that may contribute to them. Gene expression changes and epigenetic modifications induced by cocaine use and chronic abuse in humans are addressed by reviewing transcriptomic studies performed on neuronal cells and on postmortem brains. We report some genes which expression is altered by cocaine that also bear genetic risk variants for the disorder. Finally, we have a glance to the pharmacogenetics of CUD treatments, still in early stages. A better understanding of the genetic underpinnings of CUD will foster the search of effective treatments and help to move forward to personalized medicine.

PMID:34453125 | DOI:10.1038/s41380-021-01256-1

Cell Death Dis. 2021 Aug 27;12(9):812. doi: 10.1038/s41419-021-04097-6.

NO ABSTRACT

PMID:34453036 | DOI:10.1038/s41419-021-04097-6

Expert Opin Drug Metab Toxicol. 2021 Aug 27. doi: 10.1080/17425255.2021.1974398. Online ahead of print.

ABSTRACT

INTRODUCTION: Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurines, such as mercaptopurine and tioguanine (TG), fundamental chemotherapeutic agents used in the treatment of acute lymphoblastic leukemia (ALL). Polymorphisms in TPMT gene encode diminished activity enzyme, thus enhancing accumulation of active metabolites, and partially explaining the inter-individual differences in patients' clinical response.

AREAS COVERED: This review gives an overview on TPMT gene and function, and discusses the well-established pharmacogenomic implications of TPMT variants in the prevention of severe thiopurine-induced hematological toxicities and the less known implication on TG-induced sinusoidal obstruction syndrome. Additional genetic and non-genetic factors impairing TPMT activity are considered. Literature search was done in PubMed for English articles published between 1990 and June 2021, and on PharmGKB for thiopurine drugs.

EXPERT OPINION: In order to titrate thiopurines safely and effectively, achieve the right degree of lymphotoxic effect and avoid excessive myelosuppression, the optimal management will combine a pre-emptive TPMT genotyping to establish a safe initial dose to a close phenotypic monitoring of the TPMT activity and/or of the active metabolites during the long-term treatment. Compared to current ALL protocols, replacement of TG by MP during reinduction phase in TPMT heterozygotes as well as novel individualized TG regimens in maintenance for TPMT wild type subjects could be investigated to further improve outcomes while avoiding the risk of severe hepatotoxicity.

PMID:34452592 | DOI:10.1080/17425255.2021.1974398

Pharmaceuticals (Basel). 2021 Aug 21;14(8):822. doi: 10.3390/ph14080822.

ABSTRACT

Epidemiological studies have indicated that obesity is an independent risk factor for colitis and that a high-fat diet (HFD) increases the deterioration of colitis-related indicators in mice. Melatonin has multiple anti-inflammatory effects, including inhibiting tumor growth and regulating immune defense. However, the mechanism of its activity in ameliorating obesity-promoted colitis is still unclear. This study explored the possibility that melatonin has beneficial functions in HFD-induced dextran sodium sulfate (DSS)-induced colitis in mice. Here, we revealed that HFD-promoted obesity accelerated DSS-induced colitis, while melatonin intervention improved colitis. Melatonin significantly alleviated inflammation by increasing anti-inflammatory cytokine release and reducing the levels of proinflammatory cytokines in HFD- and DSS-treated mice. Furthermore, melatonin expressed antioxidant activities and reversed intestinal barrier integrity, resulting in improved colitis in DSS-treated obese mice. We also found that melatonin could reduce the ability of inflammatory cells to utilize fatty acids and decrease the growth-promoting effect of lipids by inhibiting autophagy. Taken together, our study indicates that the inhibitory effect of melatonin on autophagy weakens the lipid-mediated prosurvival advantage, which suggests that melatonin-targeted autophagy may provide an opportunity to prevent colitis in obese individuals.

PMID:34451919 | DOI:10.3390/ph14080822

Pharmaceuticals (Basel). 2021 Aug 16;14(8):804. doi: 10.3390/ph14080804.

ABSTRACT

Factors associated with olaparib toxicity remain unknown in ovarian cancer patients. The large inter-individual variability in olaparib pharmacokinetics could contribute to the onset of early significant adverse events (SAE). We aimed to retrospectively analyze the pharmacokinetic/pharmacodynamic relationship for toxicity in ovarian cancer patients from "real life" data. The clinical endpoint was the onset of SAE (grade III/IV toxicity or dose reduction/discontinuation). Plasma olaparib concentration was assayed using liquid chromatography at any time over the dosing interval. Trough concentrations (CminPred) were estimated using a population pharmacokinetic model. The association between toxicity and clinical characteristics or CminPred was assessed by logistic regression and non-parametric statistical tests. Twenty-seven patients were included, among whom 13 (48%) experienced SAE during the first six months of treatment. Olaparib CminPred was the only covariate significantly associated with increased risk of SAE onset (odds ratio = 1.31, 95%CI = [1.10; 1.57], for each additional 1000 ng/mL). The ROC curve identified a threshold of CminPred = 2500 ng/mL for prediction of SAE onset (sensitivity/specificity 0.62 and 1.00, respectively). This study highlights a significant association between olaparib plasma exposure and SAE onset and identified the threshold of 2500 ng/mL trough concentration as potentially useful to guide dose adjustment in ovarian cancer patients.

PMID:34451901 | DOI:10.3390/ph14080804

J Antimicrob Chemother. 2021 Aug 27:dkab319. doi: 10.1093/jac/dkab319. Online ahead of print.

NO ABSTRACT

PMID:34450632 | DOI:10.1093/jac/dkab319

S D Med. 2021 Jul;74(7):294-301.

ABSTRACT

INTRODUCTION: A major goal of the current personalized medicine era is to utilize pharmacogenetics (PGx) in order to influence how medications and therapies are prescribed by providers. However, disparities for prescribing medications between adults and children exist. Research has shown that children are not just small adults and there are different challenges for pediatric providers in regards to ordering and interpreting PGx tests. The goal of this study was to obtain an initial understanding of current pharmacogenetic testing by pediatric providers, as well as determine perceived barriers.

METHODS: We distributed an online survey to pediatric providers at six different institutions across the U.S.

RESULTS: Of the 252 respondents who completed the survey, 24 percent reported previously ordering PGx tests, however, over 90 percent of respondents reported they would feel more comfortable ordering and interpreting results with the assistance of a pharmacist, geneticist, genetic counselor or PGx expert. Additionally, participants identified specific barriers towards the utilization of PGx testing, as well as suggested solutions to overcome these barriers, including increasing provider education regarding testing, collaboration through a multidisciplinary team approach and established PGx programs.

CONCLUSION: As the pharmacogenetic field continues to demonstrate clinical utility in the pediatric population, it will be important to continuously identify and address barriers that exist for providers to allow for more successful implementation of PGx in the pediatric setting, as well as enhance patient care.

PMID:34449988

Pharmacy (Basel). 2021 Aug 21;9(3):146. doi: 10.3390/pharmacy9030146.

ABSTRACT

Although clinical pharmacy is a discipline that emerged in the 1960s, the question of precisely how pharmacists can play a role in therapeutic optimization remains unanswered. In the field of mental health, psychiatric pharmacists are increasingly involved in medication reconciliation and therapeutic patient education (or psychoeducation) to improve medication management and enhance medication adherence, respectively. However, psychiatric pharmacists must now assume a growing role in team-based models of care and engage in shared expertise in psychopharmacology in order to truly invest in therapeutic optimization of psychotropics. The increased skills in psychopharmacology and expertise in psychotherapeutic drug monitoring can contribute to future strengthening of the partnership between psychiatrists and psychiatric pharmacists. We propose a narrative review of the literature in order to show the relevance of a clinical pharmacist specializing in psychiatry. With this in mind, herein we will address: (i) briefly, the areas considered the basis of the deployment of clinical pharmacy in mental health, with medication reconciliation, therapeutic education of the patient, as well as the growing involvement of clinical pharmacists in the multidisciplinary reflection on pharmacotherapeutic decisions; (ii) in more depth, we present data concerning the use of therapeutic drug monitoring and shared expertise in psychopharmacology between psychiatric pharmacists and psychiatrists. These last two points are currently in full development in France through the deployment of Resource and Expertise Centers in PsychoPharmacology (CREPP in French).

PMID:34449724 | DOI:10.3390/pharmacy9030146

Diseases. 2021 Aug 12;9(3):55. doi: 10.3390/diseases9030055.

ABSTRACT

Cardiovascular disease remains the leading global cause of death. Early intervention, with lifestyle advice alongside appropriate medical therapies, is fundamental to reduce patient mortality among high-risk individuals. For those who live with the daily challenges of cardiovascular disease, pharmacological management aims to relieve symptoms and prevent disease progression. Despite best efforts, prescription drugs are not without their adverse effects, which can cause significant patient morbidity and consequential economic burden for healthcare systems. Patients with cardiovascular diseases are often among the most vulnerable to adverse drug reactions due to multiple co-morbidities and advanced age. Examining a patient's genome to assess for variants that may alter drug efficacy and susceptibility to adverse reactions underpins pharmacogenomics. This strategy is increasingly being implemented in clinical cardiology to tailor patient therapies. The identification of specific variants associated with adverse drug effects aims to predict those at greatest risk of harm, allowing alternative therapies to be given. This review will explore current guidance available for pharmacogenomic-based prescribing as well as exploring the potential implementation of genetic risk scores to tailor treatment. The benefits of large databases and electronic health records will be discussed to help facilitate the integration of pharmacogenomics into primary care, the heartland of prescribing.

PMID:34449608 | DOI:10.3390/diseases9030055

Front Pediatr. 2021 Aug 10;9:711400. doi: 10.3389/fped.2021.711400. eCollection 2021.

ABSTRACT

Objective: To investigate the impact of fetal growth restriction (FGR) on hormonal regulation of post-natal growth and glucose metabolism [via insulin and growth hormone (GH)/Insulin-like Growth factor 1 (IGF1) axis pathways] in small for gestational age (SGA) neonates. Methods: We conducted a monocentric observational prospective comparative study on 73 singleton babies born with a weight inferior to 2,000 g. We analyzed auxological (weight, height and head circumference), and hormonal (GH, IGF1, and insulin plasma concentrations) data comparing SGA and appropriate for gestational age (AGA) neonates, between day 1 and 60. Results: One third (23/73) of the neonates were SGA. Twenty-five percent (18/73) required insulin for idiopathic hyperglycemia of prematurity and were smaller in weight and head circumference at discharge. In the SGA group compared with the AGA group, GH plasma concentrations were higher at day 3 (70.1 vs. 38.0 mIU/L) and IGF1 plasma concentrations were higher at day 10 (29.0 vs. 18.7 ng/ml). Conclusions: SGA neonates displayed resistance to GH and IGF1, concomitant to insulin resistance. This could partially explain the initial defective catch-up growth and, later in life, the higher prevalence of metabolic syndrome in this population.

PMID:34447729 | PMC:PMC8382944 | DOI:10.3389/fped.2021.711400

Pharmacogenomics J. 2021 Aug 26. doi: 10.1038/s41397-021-00252-6. Online ahead of print.

ABSTRACT

BACKGROUND: A substantial number of survivors of childhood acute lymphoblastic leukemia (ALL) suffer from treatment-related late adverse effects. While multiple studies have identified the effects of chemotherapeutics and radiation therapy on musculoskeletal outcomes, few have investigated their associations with genetic factors.

METHODS: Here we analyzed musculoskeletal complications in relation to common and rare genetic variants derived through whole-exome sequencing of the PETALE cohort. Top-ranking associations were further assessed through stratified and multivariate analyses.

RESULTS: DUOX2 variant was associated with skeletal muscle function deficit, as defined by peak muscle power Z score ≤ -2 SD (P = 4.5 × 10-5 for genotyping model). Upon risk stratification analysis, common variants in the APOL3, COL12A1, and LY75 genes were associated with Z score ≤ -2 SD at the cross-sectional area (CSA) at 4% radial length and lumbar bone mineral density (BMD) in high-risk patients (P ≤ 0.01). The modulation of the effect by risk group was driven by the interaction of the genotype with cumulative glucocorticoid dose. Identified variants remained significant throughout multivariate analyses incorporating non-genetic factors of the studied cohort.

CONCLUSION: This exploratory study identified novel genetic variants associated with long-term musculoskeletal impairments in childhood ALL survivors. Replication in an independent cohort is needed to confirm the association found in this study.

PMID:34446917 | DOI:10.1038/s41397-021-00252-6

Sci Rep. 2021 Aug 26;11(1):17245. doi: 10.1038/s41598-021-96750-5.

ABSTRACT

Wound healing (WH) and cancer seem to share common cellular and molecular processes that could work in a tight balance to maintain tissue homeostasis or, when unregulated, drive tumor progression. The "Cancer Hallmarks" comprise crucial biological properties that mediate the advancement of the disease and affect patient prognosis. These hallmarks have been proposed to overlap with essential features of the WH process. However, common hallmarks and proteins actively participating in both processes have yet to be described. In this work we identify 21 WH proteins strongly linked with solid tumors by integrated TCGA Pan-Cancer and multi-omics analyses. These proteins were associated with eight of the ten described cancer hallmarks, especially avoiding immune destruction. These results show that WH and cancer's common proteins are involved in the microenvironment modification of solid tissues and immune system regulation. This set of proteins, between WH and cancer, could represent key targets for developing therapies.

PMID:34446793 | DOI:10.1038/s41598-021-96750-5