Cancers (Basel). 2022 May 13;14(10):2404. doi: 10.3390/cancers14102404.

ABSTRACT

The development of therapies that target specific disease subtypes has dramatically improved outcomes for patients with breast cancer. However, survival gains have not been uniform across patients, even within a given molecular subtype. Large collections of publicly available drug screening data matched with transcriptomic measurements have facilitated the development of computational models that predict response to therapy. Here, we generated a series of predictive gene signatures to estimate the sensitivity of breast cancer samples to 90 drugs, comprising FDA-approved drugs or compounds in early development. To achieve this, we used a cell line-based drug screen with matched transcriptomic data to derive in silico models that we validated in large independent datasets obtained from cell lines and patient-derived xenograft (PDX) models. Robust computational signatures were obtained for 28 drugs and used to predict drug efficacy in a set of PDX models. We found that our signature for cisplatin can be used to identify tumors that are likely to respond to this drug, even in absence of the BRCA-1 mutation routinely used to select patients for platinum-based therapies. This clinically relevant observation was confirmed in multiple PDXs. Our study foreshadows an effective delivery approach for precision medicine.

PMID:35626009 | DOI:10.3390/cancers14102404

Biomedicines. 2022 May 23;10(5):1210. doi: 10.3390/biomedicines10051210.

ABSTRACT

Carboplatin is the cornerstone of ovarian cancer (OC) treatment, while platinum-response, dependent on interindividual variability, is the major prognostic factor for long-term outcomes. This retrospective study was focused on explorative search of genetic polymorphisms in the Absorption, Distribution, Metabolism, Excretion (ADME) genes for the identification of biomarkers prognostic/predictive of platinum-response in OC patients. Ninety-two advanced OC patients treated with carboplatin-based therapy were enrolled at our institution. Of these, we showed that 72% of patients were platinum-sensitive, with a significant benefit in terms of OS (p = 0.001). We identified an inflammatory-score with a longer OS in patients with lower scores as compared to patients with the maximum score (p = 0.001). Thirty-two patients were genotyped for 1931 single nucleotide polymorphisms (SNPs) and five copy number variations (CNVs) by the DMET Plus array platform. Among prognostic polymorphisms, we found a potential role of UGT2A1 both as a predictor of platinum-response (p = 0.01) and as prognostic of survival (p = 0.05). Finally, we identified 24 SNPs related to OS. UGT2A1 correlates to an "inflammatory-score" and retains a potential prognostic role in advanced OC. These data provide a proof of concept that warrants further validation in follow-up studies for the definition of novel biomarkers in this aggressive disease.

PMID:35625946 | DOI:10.3390/biomedicines10051210

Biomedicines. 2022 Apr 19;10(5):940. doi: 10.3390/biomedicines10050940.

ABSTRACT

Rare diseases constitute a wide range of disorders thus defined for their low prevalence. However, taken together, rare diseases impact a considerable percentage of the world population, thus representing a public healthcare problem. In particular, neurofibromatoses are autosomal-dominant genetic disorders that include type 1 neurofibromatosis (NF1), type 2 neurofibromatosis (NF2) and schwannomatosis. Each of the three types is a genetically distinct disease with an unpredictable clinical course and for which there is still no resolutive cure. Therefore, a personalized therapeutic approach directed at improving the symptomatology as well as the search for new pharmacological strategies for the management of neurofibromatosis represents a priority for positive outcomes for affected patients. The coronavirus disease 2019 (COVID-19) pandemic has severely affected health systems around the world, impacting the provision of medical care and modifying clinical surveillance along with scientific research procedures. COVID-19 significantly worsened exchanges between healthcare personnel and neurofibromatosis patients, precluding continuous clinical monitoring in specialized clinic centers. In this new scenario, our article presents, for the first time, a comprehensive literature review on the clinical challenges for neurofibromatosis clinical care and research during the COVID-19 pandemic health emergency. The review was performed through PubMed (Medline) and Google Scholar databases until December 2021.

PMID:35625677 | DOI:10.3390/biomedicines10050940

Health Sci Rep. 2022 May 23;5(3):e650. doi: 10.1002/hsr2.650. eCollection 2022 May.

ABSTRACT

BACKGROUND AND AIMS: Lipid peroxidation end products are the major culprit for inducing chronic diseases in elderly people. Along with the elevated level of lipid peroxide biomarkers, there is a significant disruption of antioxidants balance, which combinedly propagate the diseases of elderly people. The aim of the present review is to bridge the connection of changes in lipid peroxides biomarkers and antioxidants level with age-associated diseases in elderly people.

METHODS: This narrative review was performed following a comprehensive search for suitable articles in multiple online databases, including PubMed, Google Scholar, EMBASE, Web of Science, Cochrane Library, and ScienceDirect using selected search terms. The most appropriate literature was included based on the selection criteria.

RESULTS: From the review, it is found that many age-related diseases propagated with an increased level of the end products of lipid peroxide and reduced levels of antioxidants in elderly people. When the end products of lipid peroxidation increase in the body, it creates oxidative stress, which ultimately leads to many complicated diseases, including cancers, cardiovascular and neurogenic diseases, and many other chronic inflammatory diseases. The oxidative stress induced by peroxidation can be assessed by different lipid peroxide end products such as malondialdehyde, oxidized low-density lipoprotein, isoprostanes, neuroprostanes, lipoperoxides, oxysterols (7-ketocholesterol, 7β-hydroxycholesterol), and many more.

CONCLUSIONS: This study definitively answers the correlation between the changes in lipid peroxides and antioxidants level and age-related diseases. Our narrative article recommends future investigations for elucidating the mechanisms rigorously to establish a compact correlation.

PMID:35620545 | PMC:PMC9125877 | DOI:10.1002/hsr2.650

J Trop Med. 2022 May 17;2022:3492696. doi: 10.1155/2022/3492696. eCollection 2022.

ABSTRACT

Malaria caused by the Plasmodium parasites is a major public health concern in malaria-endemic regions with P. falciparum causing the most severe form of the disease. The use of antimalarial drugs for the management of the disease proves to be one of the best methods to manage the disease. Unfortunately, P. falciparum has developed resistance to almost all the current in-use antimalarial drugs. Parasite development of resistance is primarily caused by both parasite and host genetic factors. The parasite genetic factors involve undergoing mutation in the drug target sites or increasing the drug target gene copy number to prevent the intended action of the antimalarial drugs. The host pharmacogenetic factors which determine how a particular antimalarial drug is metabolized could result in variations of drug plasma concentration and consequently contribute to variable treatment outcomes and the emergence or propagation of resistant parasites. Since both host and parasite genomes play a role in antimalarial drug action, a key question often asked is, "which of the two strongly drives or controls antimalarial drug resistance?" A major finding in our recent study published in the Malaria Journal indicates that the parasite's genetic factors rather than the host are likely to energize resistance to an antimalarial drug. However, others have reported contrary findings suggesting that the host genetic factors are the force behind resistance to antimalarial drugs. To bring clarity to these observations, there is the need for deciphering the major driving force behind antimalarial drug resistance through optimized strategies aimed at alleviating the phenomenon. In this direction, literature was systematically reviewed to establish the role and importance of each of the two factors aforementioned in the etiology of drug-resistant malaria. Using Internet search engines such as Pubmed and Google, we looked for terms likely to give the desired information which we herein present. We then went ahead to leverage the obtained information to discuss the globally avid aim of combating antimalarial drug resistance.

PMID:35620049 | PMC:PMC9129956 | DOI:10.1155/2022/3492696

Dela J Public Health. 2021 Dec 15;7(5):10-11. doi: 10.32481/djph.2021.12.005. eCollection 2021 Dec.

ABSTRACT

Advances in the field of human genetics over the past three decades have led to improvements in human health through development and availability of novel genetic testing approaches for diagnosis, prognosis, treatment therapy, safety, preventive screening and population-based risk assessment. In this commentary, I highlight the current landscape of genetic testing in Delaware with a focus on the genetic etiology and molecular diagnosis of pediatric disease, tailored treatment efficacy and safety through novel clinical trials and pharmacogenomics, and training in the application of genomic approaches to rare and common diseases. Future opportunities include integrating application of genetic information into clinical practice, improving genetics education, focusing on disparities and access, and advancing genomics and digital health technologies.

PMID:35619978 | PMC:PMC9124557 | DOI:10.32481/djph.2021.12.005

Dela J Public Health. 2021 Dec 15;7(5):12-15. doi: 10.32481/djph.2021.12.006. eCollection 2021 Dec.

ABSTRACT

Pharmacogenetics allows providers to enhance their treatment decisions for common medications used in certain conditions such as depression, gastroesophageal reflux disease (GERD), pain, and acute lymphoblastic leukemia. A precision medicine approach combines pharmacogenetics (when appropriate) with other clinical and environmental factors to minimize trial-and-error of treatment. Public awareness of the impact of pharmacogenetics on treatment decisions is growing, and healthcare should be aware of the resources supporting it. Pharmacogenetics may seem daunting, but the accessibility of pharmacogenetic testing has improved with growing availability of evidence-based clinical recommendations, pharmacogenetic tests, clinical decision support resources, insurance coverage, and digestible education materials. As precision medicine and precision public health expands over the next decade, pharmacogenetic testing will continuously grow to be cheaper and part of routine genetic or genomic screenings, and be another common test-like liver or kidney function tests-that can enhance treatment decisions.

PMID:35619975 | PMC:PMC9124564 | DOI:10.32481/djph.2021.12.006

Front Immunol. 2022 May 10;13:853403. doi: 10.3389/fimmu.2022.853403. eCollection 2022.

ABSTRACT

Aldosterone-producing adenoma (APA) is a benign adrenal tumor that results in persistent hyperaldosteronism. As one major subtype of primary aldosteronism, APA leads to secondary hypertension that is associated with immune dysregulation. However, how the adaptive immune system, particularly the T-cell population, is altered in APA patients remains largely unknown. Here, we performed TCR sequencing to characterize the TCR repertoire between two age-matched groups of patients: one with APA and the other one with essential hypertension (EH). Strikingly, we found a significant reduction of TCR repertoire diversity in the APA group. Analyses on TCR clustering and antigen annotation further showed that the APA group possessed lower diversity in TCR clonotypes with non-common antigen-specific features, compared with the EH group. In addition, our results indicated that the strength of correlation between generation probabilities and frequencies of TCR clonotypes was significantly higher in the APA group than that in the EH group. Finally, we observed that clinical features, including plasma aldosterone level, aldosterone-renin ratio, and blood sodium level, were positively associated with the strength of correlation between generation and abundance of TCR clonotypes in the APA group. Our findings unveiled the correlation between T-cell immune repertoire and APA, suggesting a critical role of such adrenal adenoma in the T-cell immunity of patients with hypertension.

PMID:35619691 | PMC:PMC9127864 | DOI:10.3389/fimmu.2022.853403

Methods Mol Biol. 2022;2485:111-131. doi: 10.1007/978-1-0716-2261-2_8.

ABSTRACT

Micro-heart muscle arrays enable medium-throughput experiments to model the cardiac response to a variety of environmental and pharmaceutical effects. Here, we describe stem cell culture maintenance, methods for successful cardiac differentiation, and formation of micro-heart muscle arrays for electrophysiology and molecular biology assays.

PMID:35618902 | DOI:10.1007/978-1-0716-2261-2_8

Semin Nephrol. 2022 Jan;42(1):86-98. doi: 10.1016/j.semnephrol.2022.01.001.

ABSTRACT

The article focuses on immunosuppression pharmacology, adverse-event profile, clinical efficacy, and, when available, pharmacogenomic data.

PMID:35618398 | DOI:10.1016/j.semnephrol.2022.01.001

Pharmacogenomics. 2022 May 26. doi: 10.2217/pgs-2022-0022. Online ahead of print.

ABSTRACT

Aim: Hepatotoxicity is a known adverse effect of antituberculosis drugs. The NAT2 gene polymorphism has been associated with an increased risk of antituberculosis drug-induced hepatotoxicity (ATDIH). Materials and methods: This study investigates the association of NAT2 polymorphism and clinical risk factors that may contribute to the development of ATDIH. The authors sequenced the NAT2 region of 33 tuberculosis patients who developed ATDIH and 100 tuberculosis patients who did not develop ATDIH during tuberculosis treatment. NAT2 haplotypes were inferred and NAT2 acetylator status was predicted from the combination of the inferred haplotypes. Multiple logistic regression was performed to identify possible factors that are associated with ATDIH. Results: The TT genotype of NAT2*13A and the AA genotype of NAT2*6B were found to be substantially linked with the risk of ATDIH, with odds ratios of 3.09 (95% CI: 1.37-6.95) and 3.07 (95% CI: 1.23-7.69), respectively. NAT2 slow acetylators are 3.39-times more likely to develop ATDIH. Factors that were associated with ATDIH include underlying diabetes mellitus (adjusted odds ratio [AOR] 2.96; 95% CI: 1.05-8.37), pre-treatment serum bilirubin (AOR 1.09; 95% CI: 1.02-1.16) and NAT2 slow acetylator (AOR 3.77; 95% CI: 1.51-9.44). Conclusion: Underlying diabetes mellitus, having a higher baseline bilirubin and being a slow acetylator are identified as the risk factors associated with ATDIH among patients in Malaysia.

PMID:35615896 | DOI:10.2217/pgs-2022-0022

J Pharm Policy Pract. 2022 May 25;15(1):39. doi: 10.1186/s40545-022-00435-x.

ABSTRACT

OBJECTIVES: To evaluate knowledge, attitude and perception of community pharmacists towards pharmacogenomics services.

METHODS: A cross-sectional study was conducted among community pharmacists in two cities in Northern Nigeria using a self-administered, validated and pre-tested questionnaire. The data were collected from December 2021 to February 2022 and were analysed using both descriptive and inferential analyses.

RESULTS: A total of 161 completed questionnaires were included in this study (response rate was 61.9%). Most of the respondents were males (59.0%). Only 25.5% had previous pharmacogenomics training but 90.1% indicated an interest in attending pharmacogenomics training in the future. Overall, respondents had moderate knowledge of pharmacogenomics with higher knowledge score found among those who had previous pharmacogenomics training (11.9 ± 1.7 vs 10.5 ± 2.4; p = 0.001), and those with postgraduate qualification (11.7 ± 1.9 vs 10.7 ± 2.3; p = 0.028). The mean attitude score was 6.8 ± 2.0 out of 10.0 indicating a good attitude towards pharmacogenomics services. Those with previous training (8.1 ± 1.7 vs 6.2 ± 1.9; p < 0.001) and those with postgraduate qualification (7.2 ± 2.3 vs 6.6 ± 1.9; p = 0.042) had better attitude towards pharmacogenomics services. The median perception score was 34.0 out of 45.0, indicating a positive perception towards pharmacogenomics. There was a better perception among those with previous pharmacogenomics training (40.0 [21-45] vs 34.0 [0-45]; p = 0.002) and those with postgraduate qualifications (39.0 [0-45] vs 34.0 [21-45]; p = 0.010). Barriers to the implementation of pharmacogenomics included lack of knowledge (89.4%), lack of guidelines (87.5%) and lack of reimbursement (81.4%).

CONCLUSION: Community pharmacists have a moderate knowledge, a good attitude and a positive perception towards pharmacogenomics services. Those with previous pharmacogenomics training and those with postgraduate qualifications had better knowledge, attitude and perception towards pharmacogenomics services. Lack of knowledge, lack of guidelines and lack of reimbursement were the major barriers to the implementation of pharmacogenomics services in community pharmacies in Nigeria. Pharmacogenomics should be included in pharmacy training curricula to prepare pharmacists for the provision of pharmacogenomics services. Development of local guidelines and a robust reimbursement plan for pharmacogenomics services is recommended.

PMID:35614463 | DOI:10.1186/s40545-022-00435-x

NPJ Genom Med. 2022 May 25;7(1):32. doi: 10.1038/s41525-022-00304-1.

ABSTRACT

Transient-receptor potential (TRP) channels comprise a diverse family of ion channels, which play important roles in regulation of intracellular calcium. Emerging evidence has revealed the critical roles of TRP channels in tumor development and progression. However, we still lack knowledge about the genetic and pharmacogenomics landscape of TRP genes across cancer types. Here, we comprehensively characterized the genetic and transcriptome alterations of TRP genes across >10,000 patients of 33 cancer types. We revealed prevalent somatic mutations and copy number variation in TRP genes. In particular, mutations located in transmembrane regions of TRP genes were likely to be deleterious mutations (p-values < 0.001). Genetic alterations were correlated with transcriptome dysregulation of TRP genes, and we found that TRPM2, TRPM8, and TPRA1 showed extent dysregulation in cancer. Patients with TRP gene alterations were with significantly higher hypoxia scores, tumor mutation burdens, tumor stages and grades, and poor survival. The alterations of TRP genes were significantly associated with the activity of cancer-related pathways. Moreover, we found that the expression of TRP genes were potentially useful for development of targeted therapies. Our study provided the landscape of genomic and transcriptomic alterations of TPRs across 33 cancer types, which is a comprehensive resource for guiding both mechanistic and therapeutic analyses of the roles of TRP genes in cancer. Identifying the TRP genes with extensive genetic alterations will directly contribute to cancer therapy in the context of predictive, preventive, and personalized medicine.

PMID:35614079 | DOI:10.1038/s41525-022-00304-1

JMA J. 2022 Apr 15;5(2):177-189. doi: 10.31662/jmaj.2021-0156. Epub 2022 Mar 11.

ABSTRACT

INTRODUCTION: Pharmacogenomic (PGx) testing results provide valuable information on drug selection and appropriate dosing, maximization of efficacy, and minimization of adverse effects. Although the number of large-scale, next-generation-sequencing-based PGx studies has recently increased, little is known about the risks and benefits of returning PGx results to ostensibly healthy individuals in research settings.

METHODS: Single-nucleotide variants of three actionable PGx genes, namely, MT-RNR1, CYP2C19, and NUDT15, were returned to 161 participants in a population-based Tohoku Medical Megabank project. Informed consent was obtained from the participants after a seminar on the outline of this study. The results were sent by mail alongside sealed information letter intended for clinicians. As an exception, genetic counseling was performed for the MT-RNR1 m.1555A > G variant carriers by a medical geneticist, and consultation with an otolaryngologist was encouraged. Questionnaire surveys (QSs) were conducted five times to evaluate the participants' understanding of the topic, psychological impact, and attitude toward the study.

RESULTS: Whereas the majority of participants were unfamiliar with the term PGx, and none had undergone PGx testing before the study, more than 80% of the participants felt that they could acquire basic PGx knowledge sufficient to understand their genomic results and were satisfied with their potential benefit and use in future prescriptions. On the other hand, some felt that the PGx concepts or terminology was difficult to fully understand and suggested that in-person return of the results was desirable.

CONCLUSIONS: These results collectively suggest possible benefits of returning preemptive PGx information to ostensibly healthy cohort participants in a research setting.

PMID:35611229 | PMC:PMC9090545 | DOI:10.31662/jmaj.2021-0156

Biochem Biophys Res Commun. 2022 May 18;615:75-80. doi: 10.1016/j.bbrc.2022.05.055. Online ahead of print.

ABSTRACT

Nuclear receptor Pregnane X Receptor (PXR; NR1I2) has transcriptional regulation functions for energy homeostasis in the liver. Mouse PXR has a conserved phosphorylation motif at serine 347 (serine 350 in humans) within the ligand-binding domain. PXR phosphorylated at this motif is expressed in mouse livers in response to fasting. Mice with a PXR∗Ser347Ala knockin mutation (PXR KI) were generated to block phosphorylation, and utilized to investigate the role of Ser347 phosphorylation in vivo. PXR KI mice had decreased body weight at 8-weeks of age and had much greater weight loss after fasting compared with PXR WT mice. The cDNA microarray analysis of hepatic mRNAs showed that cell death or apoptotic signaling was induced in fasting PXR KI mice. Moreover, increasing hepatic lipids, triglycerides and the development of hypertriglyceridemia were observed in fasting PXR KI mice. These findings are indicative that blocking phosphorylation prevents mice from maintaining hepatic energy homeostasis. Thus, phosphorylated PXR may be an essential factor to prevent the liver from developing damage caused by fasting.

PMID:35609418 | DOI:10.1016/j.bbrc.2022.05.055

Am J Health Syst Pharm. 2022 May 24:zxac147. doi: 10.1093/ajhp/zxac147. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: Results of the 2021 ASHP National Survey of Pharmacy Practice in Hospital Settings are presented.

METHODS: Pharmacy directors at 1,498 general and children's medical/surgical hospitals in the United States were surveyed using a mixed-mode method of contact by email and mail. Survey completion was online. IQVIA supplied data on hospital characteristics; the survey sample was drawn from IQVIA's hospital database.

RESULTS: The response rate was 21.9%. Pharmacists are routinely assigned to a majority of patients at least 8 hours per day, 5 days per week in 70.4% of hospitals. This is an increase from 60.8% in 2018 and has steadily increased over the past decade. Pharmacists independently prescribe medications pursuant to a diagnosis in 30.9% of hospitals, an increase from 21.1% in 2020. Pharmacists have prescribing authority in 67% of health-system ambulatory clinics and can recommend or schedule pharmacogenomics testing for drug and dosage selection in 11.4% of hospitals, an increase from 5.4% in 2019. Pharmacists are using electronic methods in 82.5% of hospitals to collect information for monitoring medication therapy. Shortages of entry-level pharmacy technicians are acute, with 73.4% of survey respondents reporting a shortage. Technician shortages have affected pharmacy operations and have prompted new recruitment and retention strategies.

CONCLUSION: Despite workforce challenges, clinical pharmacy services continue to expand to cover increasing numbers of patients with medication management services in both the inpatient and outpatient settings. The use of data analytics and pharmacy technicians has contributed to this evolution. Addressing the workforce challenges will be critical to sustain this progress.

PMID:35609002 | DOI:10.1093/ajhp/zxac147

Pharmacogenomics. 2022 May 24. doi: 10.2217/pgs-2022-0014. Online ahead of print.

ABSTRACT

Background: Vitamin K antagonists (VKAs) are class I oral anticoagulants that are widely prescribed following surgical heart valve implantation. The objective of this study was to quantify the relative effects of VKORC1, CYP2C9 and CYP4F2 genotypes in predicting VKA dosing. Materials & methods: A total of 506 South Indian patients with mechanical prosthetic heart valves who were prescribed oral VKAs, such as warfarin or acenocoumarol, were genotyped. The discriminatory ability of mutant genotypes to predict dose categories and bleeding events was assessed using regression analysis. Results: The VKORC1 rs9923231, CYP2C9*3 and CYP4F2*3 mutant genotypes significantly influenced VKA-dose requirements and explained 27.47% of the observed dose variation. Conclusion: These results support pharmacogenetic screening for initial VKA dosing among South Indian patients with mechanical prosthetic heart valves.

PMID:35608144 | DOI:10.2217/pgs-2022-0014

Anal Methods. 2022 May 24. doi: 10.1039/d2ay00129b. Online ahead of print.

ABSTRACT

Doxepin, a tricyclic antidepressant (TCA), is widely used in the treatment of depressive disorder and anxiety. There are some liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that have been reported for detecting doxepin, but inadequacies in recovery and cumbersome sample preparation obstruct the pharmacokinetics study. Therefore, we aimed to develop and validate a rapid sample preparation method based on solid-phase extraction (SPE) for the precise quantification of doxepin and its metabolites. Chromatography separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) and a mobile phase consisting of 70% of mobile phase A (0.1% formic acid and 10 mM ammonium formate) and 30% mobile phase B (0.1% formic acid in acetonitrile) at a flow rate of 0.4 mL min-1 in the step gradient elution conditions. The lower limits of quantification for doxepin and N-nordoxepin were 4 pg mL-1 and 2 pg mL-1, respectively. This method was validated with satisfactory results including good precision and accuracy. A rapid, sensitive, and specific LC-MS/MS method was developed and validated for the determination of doxepin in human plasma. This method could be applied for determining doxepin and N-nordoxepin concentrations in plasma that could be useful for bioequivalence study of 3 mg doxepin.

PMID:35608048 | DOI:10.1039/d2ay00129b

Expert Rev Anti Infect Ther. 2022 May 24. doi: 10.1080/14787210.2022.2081546. Online ahead of print.

ABSTRACT

INTRODUCTION: Tuberculosis (TB) is a transnational public health concern, which requires more precise treatment strategies than the existing approaches. Vitamin D modulates the inflammatory and immune response to the disease. Robust evidence shows that vitamin D deficiency and its receptor gene polymorphism influence the susceptibility to TB and the outcome of the anti-tubercular treatment (ATT). However, in the different populations, these findings were inconsistent and even contradictory.

AREAS COVERED: The current review focuses on the association between vitamin D receptor (VDR) gene polymorphism with the risk of development of TB disease and response to the ATT. Additionally, it reviews various systematic reviews and meta-analyses on the impact of vitamin D supplements on both clinical and treatment outcomes in TB patients.

EXPERT OPINION: Although the majority of the findings rule out the benefits of the supplementation, sufficient evidence is available to warrant larger epidemiological research that should be aimed to generate possible interaction among the VDR polymorphism, vitamin D status, and the outcome in TB. We conclude that establishing such an association in different ethnic populations will help design nutrigenomics- or pharmacogenomics-based vitamin D supplementation to develop a personalized medicine approach to flatten the curve of TB disease.

PMID:35608034 | DOI:10.1080/14787210.2022.2081546

Pharmacogenomics. 2022 May 24. doi: 10.2217/pgs-2022-0011. Online ahead of print.

ABSTRACT

Talazoparib is an oral PARP inhibitor approved for locally advanced/metastatic breast cancer. There is no consensus, however, as to whether it is better used as a first-line treatment or after other therapies in patients with gBRCA mutations. In fact, talazoparib showed its superiority compared with chemotherapy in the survival and quality of life of patients with BRCA mutations, with an acceptable toxicity profile. While it's role in this indication is not debated, it's cost as well as the availability of other effective new agents, particularly immune checkpoint inhibitors, may encourage the movement of this drug to later treatment lines. Until more robust data are available, the best treatment sequence for BRCA-mutated breast cancer must be personalized on a case-by-case basis.

PMID:35607887 | DOI:10.2217/pgs-2022-0011