Personalized Medicine

Evaluating the impact of infectious disease pharmacy services on voriconazole dose individualization in pediatric oncology
Azab MS, Makhlouf D, Ahmed O, Hassanain O, Shalaby L and Nagy M
The application of personalized medication management for Voriconazole(VCZ), such as therapeutic drug monitoring (TDM), is the gold standard for attaining therapeutic goals in invasive fungal infections. Infectious disease (ID) pharmacists are the best for ensuring the recommendations are properly implemented.
Leveraging oncology clinical case report data through the Cancer Knowledgebase (CKB)
Gokhale RH, Statz CM, Yin T, Russell RP, Edie S, Lehman CE and Patterson SE
Clinical case reports in oncology are an untapped resource of patient data that include relationships between molecular alterations, tumor types, and response to targeted therapy. A current challenge to widespread utilization of case reports in clinical practice is the lack of systematic organization of clinical evidence across disease types, patient outcomes, therapies, and associated molecular features. To address this challenge, we sought to demonstrate the utility of Cancer Knowledgebase (CKB) (https://ckb.genomenon.com/) in interpreting oncology case report data for health care providers.
Polygenic risk scores to refine Breast cancer screening and prevention strategies
Roberts E, Flaum N, Howell SJ and Evans D
Breast cancer (BC) is the world's most prevalent cancer and can affect almost any post-pubertal woman. Early detection is associated with improved survival, and most high-income countries have adopted population-based screening programs to enhance early detection and survival although significant differences in screening age, methodology, and frequency exist. BC is known to be a heritable disease, with a small percentage of women having pathogenic variants in moderate or high-risk genes. However, Polygenic Risk Scores (PRS) incorporate many low penetrance single nucleotide polymorphisms (SNPs) and are the most powerful tool to help stratify women based on their personalized BC risk. PRS are particularly useful if incorporated into established risk prediction models (RPM). Risk stratification using PRS-containing RPMs can guide eligibility for enhanced screening and prevention programmes. This review discusses the role PRS plays in personalized risk prediction screening and prevention approaches as some of the challenges to their use.
Correction
MYC variant at 8q24 increases susceptibility to urinary bladder cancer: a meta-analysis of 53,957 individuals
de Moraes FCA, Rego LHRM, Morbach V, de Lima MPP and Burbano RMR
Urinary bladder cancer (UBC), the tenth most common globally with a male predominance, has its risk factors like smoking and single nucleotide polymorphisms (SNPs), yet the MYC gene's role, especially the rs9642880 GT/TT polymorphism on chromosome 8q24.21, in cancer susceptibility is underexplored.
A multilevel ensemble model for predicting mutation types in bladder cancer
Jain A, Dey S, Garg D, Singh H, Pattanaik S, Mavuduru RS and Rana PS
In urinary bladder cancer, early diagnosis plays a key role for effective patient management. Moreover, accurate prediction of genetic mutations plays a critical role in identifying biomarkers for prognosis and therapy.
How to treat BRAF mutant metastatic melanoma?
Sini MC, Casula M, Pisano M, Palmieri G and Manca A
Melanoma is a malignant tumour arising from melanocytes and is the most aggressive type of skin cancer. In advanced disease standard treatments are largely ineffective. About 40% of cutaneous melanomas carry BRAF mutations-more common in younger patients-and these are linked to more aggressive behaviour and a higher risk of brain metastasis. Over the past decade, targeted therapies (TT) using BRAF and MEK inhibitors (BRAFi, MEKi), along with immune checkpoint inhibitors (ICI), have significantly improved response rates and survival in metastatic melanoma.
Tailoring pediatric vancomycin doses: achieving therapeutic levels and minimizing toxicity in oncology patients
Hossam N, Makhlouf D, Elzeiny A, Elzeiny A, Kamal S, Hassanien O, Shalaby L and Nagy M
Vancomycin is a widely used nephrotoxic drug in pediatric oncology. Our aim was to assess the initial vancomycin dosing protocols required for achieving the target therapeutic concentrations of vancomycin between 10 and 20 mcg/ml.
Optimizing breast cancer therapy: chemoressitance and machine learning for precision prediction
Lichtenfels M, Dalmolin MGS, Marcolin JC, Resende H, Borba Anton de Souza A, Silva Marques B, Fontana V, Hickmann Nyland F, Casales Schorr M, Miranda I, Kobe L, da Silva CA, Ac Fernandes M, Brunetto de Farias C, Frasson AL and Pedrini JL
Validate a novel in vitro resistance platform for breast cancer (BC) by assessing resistance profiles of treatment-naïve and residual tumors after neoadjuvant chemotherapy (NACT) and applying a machine learning algorithm to predict NACT response using clinical biomarkers.
Patient-Derived Tumour Organoids (PDOs) may help oncologists in clinical practice
Brandi R, Palcau AC, Migliano E, Strano S and Blandino G
The use of cancer organoids represents a major advancement in oncology research, addressing the limitations of traditional 2D cell cultures. Optimized protocols now allow the generation of organoids from a wide range of tumor types, including breast, skin, lung, head and neck, and endometrial cancers. These three-dimensional models more accurately replicate the architecture and complexity of patient tumors compared to 2D cultures, spheroids derived from cell lines, or Patient-Derived Tumor Organoids (PDOs) xenografts (PDTXs). This improved fidelity is largely due to the inclusion of the tumor microenvironment (TME) and the potential for immune system interactions, as shown in studies involving co-cultures with peripheral blood mononuclear cells (PBMCs). Patient-Derived Tumor Organoids (PDOs) organoids (PDOs) have emerged as a powerful platform for preclinical testing, enabling the prediction of patient-specific responses to therapies prior to clinical application. Furthermore, PDOs support the discovery of novel biomarkers and the establishment of biobanks, offering valuable insights into cancer biology and helping to overcome persistent challenges in the field. In this context, we will discuss the methods for generating PDOs, the critical role of selecting appropriate culture media and growth factors tailored to different tumor types, and the analytical techniques to verify the extent to which PDOs recapitulate the original tumor tissue.
A scoping review of the cost-effectiveness of precision treatment in chronic lymphocytic leukemia
Punian J, Ehman M, Weymann D and Regier DA
Chronic lymphocytic leukemia (CLL) is a common, incurable leukemia. Precision treatment for CLL uses genetic testing to align therapeutic selection with patient characteristics. Insurers are uneven in their reimbursement of precision CLL treatment, partly due to uncertain evidence of cost-effectiveness. This review surveys the current cost-effectiveness evidence for precision CLL treatment and identifies areas for future research. We conducted a scoping review of economic evaluations of precision CLL treatments indexed in PubMed, Embase, and Web of Science and published by October 2024. Eight articles were retrieved. Studies examined heterogeneous patient populations, treatment regimens, and stratification strategies. Four studies (50%) focused on subgroups with del(17p) and/or TP53 mutations only. Three studies (38%) analyzed the costs and outcomes of both treatment and genetic testing, while 62% did not include the cost or outcomes of genetic testing. All studies obtained clinical model parameters from published trials. Five studies (63%) reported that precision CLL treatment was likely cost-effective at willingness to pay thresholds ranging from $26,489/QALY to $130,477/QALY. Future research should focus on generating real-world data, broadening the scope of analysis to include societal perspectives, and exploring distributional impacts to more effectively address the heterogeneity of precision CLL treatments when determining their cost-effectiveness.
Association of miR-21 rs1292037 polymorphism with congenital heart disease susceptibility in Chinese children
Tang H, Zhang W, Xu D and Xu J
Congenital heart disease (CHD) is a condition characterized by structural or functional abnormalities of the cardiovascular system present at birth. This study investigated the correlation between microRNA-21 (miR-21) rs1292037 and rs13137 polymorphisms and children with CHD.
A rare likely pathogenic HLA-DRB1 variant with compromised immunity in severe COVID-19 patient and in-hospital mortality
Mir R, Alsayed BA and Fahad Ullah M
The severity of COVID-19 disease can vary greatly, influenced by genetic factors and comorbid conditions that may increase mortality. This study has examined potential genetic influences on the disease for a young adult aged 36 years with T2DM-CAD multi-morbidity with severe COVID-19 disease and in-hospital mortality using whole-exome sequencing. The patient exhibited a constellation of severe symptoms and abnormality in several biochemical markers associated with COVID-19 disease and comorbid conditions. A total of 756 variants were discovered in the patient, including several rare and novel variants associated with immune pathways. A set of 10 unique candidate variants in 10 distinct genes were identified with nine variants located within genes associated with the COVID-19 panel (HLA-DRB1, IL23R, PRKDC, RNF31, SLC37A4, TAP2, TCIRG1, TCN2, and TPP2), while one variant was found in a gene (PAX6) from Diabetes panel. Enrichment analysis showed that the top three enriched GO biological processes were a response to stimulus ( = 23,  = 6.8E-3), immune system process ( = 22,  = 3.6E-12), and regulation of immune system process ( = 19,  = 1.57E-11). The Maximal Clique Centrality algorithm identified HLA-DRB1 as a prominent hub gene and potential loss-of-function mutation in HLA-DRB1, suggests a compromised antigen presentation mechanism within this patient.
Awareness, and interest in personalized medicine: a cross-sectional survey study of health professionals
Mostafaei A, Rahmani A, Shahsavarinia K, Harzand-Jadidi S, Milanchian N, Rahmati F, Salehi-Pourmehr H and Hajebrahimi S
Personalized medicine (PM) is advancing disease prevention and treatment, but regulatory and clinical concerns persist, requiring evaluation of healthcare professionals' (HPs) knowledge and attitudes.
Evaluation of pharmacogenomic information in drug labeling: a case study from Jordan
Jarrar Y, Hakooz N, Ajamieh MA, Shawagfeh K, Zaidan R and Al Shareef O
Pharmacogenomics (PGx) examines how genetic variations influence individual responses to medications, enabling more precise drug and dose selection. Drug labeling communicates PGx information to healthcare providers. However, in many countries, including Jordan, PGx integration into clinical practice remains limited.
Navigating ethical problems of commercialization: towards inclusive organoid research
van Daal M and Jongsma KR
Organoids are three-dimensional, self-organizing cell structures grown from human biospecimens that allow researchers to study development, disease, and drug responses. Organoid technology holds promise for precision medicine, as it can tailor therapies to specific individuals. Including diverse groups within organoid research is essential to collect representative data for the development of treatments for all populations and to reduce health disparities. Commercial parties are increasingly involved in organoid research. The involvement of such parties can negatively affect the ways in which underrepresented groups are included and recruited and can affect their willingness to donate their biospecimen. In this paper, we argue that commercial involvement in organoid research poses three problems that can hinder the equal representation of groups or the equitable access to treatments derived from organoid research. First, commercially driven organoid research presents challenges to the informed consent process. Second, commercial involvement can undermine trust among underrepresented groups and reduce their willingness to donate biospecimens. Third, benefit sharing becomes ethically more complex when profits are generated and underrepresented groups are involved. Therefore, researchers and commercial parties should actively address these challenges by (re)establishing trust, using transparent and inclusive communication, ensuring ongoing reciprocity, and uphold shared responsibility.
Leveraging circulating microRNAs for personalized disease-modifying therapies in type 1 diabetes
Grieco GE, Dotta F and Sebastiani G
Type 1 Diabetes (T1D) is a chronic autoimmune disease marked by the progressive immune-mediated destruction of insulin-producing pancreatic beta-cells. The clinical management of T1D is complicated by its heterogeneity and the variability in individual responses to treatment. Personalized medicine has emerged as a promising strategy to address these challenges by tailoring interventions to individual patient profiles. Circulating microRNAs (miRNAs) - small, non-coding RNAs found in bodily fluids - represent potential biomarkers across various diseases, including T1D. This review examines the role of circulating miRNAs in advancing personalized medicine for T1D, emphasizing on their application in the response prediction of innovative therapeutic strategies. We discuss key miRNAs -detectable in blood plasma- implicated in modulating immune responses and beta-cell function and associated with patient-specific differences in disease onset, progression, and therapeutic responses, underscoring their potential in refining treatment strategies. We explore how miRNA signatures can enhance clinical decision-making by predicting disease progression, assessing susceptibility to complications, and monitoring responses to newly proposed therapies, thus leveraging these more precise and individualized treatment regimens, improving the effectiveness and outcomes of T1D management. The integration of circulating miRNAs into personalized treatment frameworks represents a transformative opportunity to advance T1D care and improve patients' outcomes.
Ready to test your DNA? Public acceptance of genetic testing in the precision medicine era among Chinese residents
Wang G, Pang C, Wang Q, Chen Z and Su Z
This study aimed to explore the Chinese public's experiences with, perceptions of, attitudes toward, and willingness to use genetic testing (GT) in the precision medicine era.
Gastric cancer risk and BRCA1/2 mutations: a systematic review and meta-analysis
de Moraes FCA, Matheus GTFU, Souza MEC and Burbano RMR
Gastric cancer is an aggressive and heterogeneous disease, primarily sporadic, with only 1-3% of cases being hereditary. However, gastric cancer is a component of several hereditary cancer syndromes. The BRCA1 and BRCA2 genes encode key DNA repair proteins involved in homologous recombination. Studies suggest a significantly increased risk of gastric cancer in first-degree relatives of BRCA1/2 mutation carriers.
Effect of miRNA gene polymorphisms on prostate cancer susceptibility: a case-control study and an updated meta-analysis
Sharma S, Gupta R, Raina JK, Loona S, Kour T, Kumar P and Panjaliya RK
Prostate cancer (CaP) is the most commonly diagnosed malignant tumor and the leading cause of cancer-related deaths among men. Due to their potential functional significance, microRNA genes are considered promising candidates for identifying cancer-related genetic biomarkers. This study investigates the association between microRNA-196a2 (rs11614913), microRNA-146a (rs2910164), and microRNA-149 (rs2292832) and the risk of prostate cancer among males in the Jammu region of Jammu and Kashmir (J&K).
Val66Met polymorphism in the BDNF gene and antidepressant response in depression: an updated meta-analysis
Tiongco RE, Arbas R, Caguiat A, Castro EJ, Dela Cruz KC, Dominguez MJ, Guintu MAA, Mercado JA and Vallo J
The polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been linked to antidepressant treatment response in patients with major depressive disorder (MDD), yet findings remain inconclusive. This updated meta-analysis aimed to clarify this association and explore subgroup effects based on antidepressant class and treatment duration.