Displaying publications 21 - 40 of 73 in total

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  1. Fulltext Advancing Personalized Medicine Through the Application of Whole Exome Sequencing and Big Data Analytics
    Suwinski P, Ong C, Ling MHT, Poh YM, Khan AM, Ong HS
    Front Genet, 2019;10:49.
    PMID: 30809243 DOI: 10.3389/fgene.2019.00049
    There is a growing attention toward personalized medicine. This is led by a fundamental shift from the 'one size fits all' paradigm for treatment of patients with conditions or predisposition to diseases, to one that embraces novel approaches, such as tailored target therapies, to achieve the best possible outcomes. Driven by these, several national and international genome projects have been initiated to reap the benefits of personalized medicine. Exome and targeted sequencing provide a balance between cost and benefit, in contrast to whole genome sequencing (WGS). Whole exome sequencing (WES) targets approximately 3% of the whole genome, which is the basis for protein-coding genes. Nonetheless, it has the characteristics of big data in large deployment. Herein, the application of WES and its relevance in advancing personalized medicine is reviewed. WES is mapped to Big Data "10 Vs" and the resulting challenges discussed. Application of existing biological databases and bioinformatics tools to address the bottleneck in data processing and analysis are presented, including the need for new generation big data analytics for the multi-omics challenges of personalized medicine. This includes the incorporation of artificial intelligence (AI) in the clinical utility landscape of genomic information, and future consideration to create a new frontier toward advancing the field of personalized medicine.
    Matched MeSH terms: Precision Medicine
  2. Proteome Heterogeneity in Colorectal Cancer
    Lim LC, Lim YM
    Proteomics, 2018 02;18(3-4).
    PMID: 29316255 DOI: 10.1002/pmic.201700169
    Tumor heterogeneity is an important feature of colorectal cancer (CRC) manifested by dynamic changes in gene expression, protein expression, and availability of different tumor subtypes. Recent publications in the past 10 years have revealed proteome heterogeneity between different colorectal tumors and within the same tumor site. This paper reviews recent research works on the proteome heterogeneity in CRC, which includes the heterogeneity within a single tumor (intratumor heterogeneity), between different anatomical sites at the same organ, and between primary and metastatic sites (intertumor heterogeneity). The potential use of proteome heterogeneity in precision medicine and its implications in biomarker discovery and therapeutic outcomes will be discussed. Identification of the unique proteome landscape between and within individual tumors is imperative for understanding cancer biology and the management of CRC patients.
    Matched MeSH terms: Precision Medicine
  3. Recent progress of targeted nanocarriers in diagnostic, therapeutic, and theranostic applications in colorectal cancer
    Choudhury H, Pandey M, Saravanan V, Mun ATY, Bhattamisra SK, Parikh A, et al.
    Biomater Adv, 2023 Oct;153:213556.
    PMID: 37478770 DOI: 10.1016/j.bioadv.2023.213556
    Cancer at the lower end of the digestive tract, colorectal cancer (CRC), starts with asymptomatic polyps, which can be diagnosed as cancer at a later stage. It is the fourth leading cause of malignancy-associated mortality worldwide. Despite progress in conventional treatment strategies, the possibility to overcome the mortality and morbidity issues with the enhancement of the lifespan of CRC patients is limited. With the advent of nanocarrier-based drug delivery systems, a promising revolution has been made in diagnosis, treatment, and theranostic purposes for cancer management. Herein, we reviewed the progress of miniaturized nanocarriers, such as liposomes, niosomes, solid lipid nanoparticles, micelles, and polymeric nanoparticles, employed in passive and active targeting and their role in theranostic applications in CRC. With this novel scope, the diagnosis and treatment of CRC have proceeded to the forefront of innovation, where specific characteristics of the nanocarriers, such as processability, flexibility in developing precise architecture, improved circulation, site-specific delivery, and rapid response, facilitate the management of cancer patients. Furthermore, surface-engineered technologies for the nanocarriers could involve receptor-mediated deliveries towards the overexpressed receptors on the CRC microenvironment. Moreover, the potential of clinical translation of these targeted miniaturized formulations as well as the possible limitations and barriers that could impact this translation into clinical practice were highlighted. The advancement of these newest developments in clinical research and progress into the commercialization stage gives hope for a better tomorrow.
    Matched MeSH terms: Precision Medicine
  4. Fulltext Qualitative assessment of knowledge, attitude and practice of oncologists about precision medicine in cancer patients- study from Lahore, Pakistan
    Naaem R, Hashmi FK, Yaqub S, Mohamed Noor DA
    PLoS One, 2024;19(4):e0299010.
    PMID: 38578776 DOI: 10.1371/journal.pone.0299010
    BACKGROUND: Precision medicine (PM) is in great progressive stages in the West and allows healthcare practitioners (HCPs) to give treatment according to the patient's genetic findings, physiological and environmental characteristics. PM is a relatively new treatment approach in Pakistan Therefore, it is important to investigate the level of awareness, attitude, and challenges faced by oncology physicians while practicing PM for various therapies, especially cancer treatment.

    OBJECTIVES: The present study aims to explore the level of awareness, attitude, and practice of PM in Pakistan along with the challenges faced by the oncologists for the treatment of cancer using the PM approach.

    METHODS: Phenomenology-based qualitative approach was used. Face-to-face in-depth interviews were conducted using the purposive sampling approach among oncologists in Lahore, Pakistan. The data were analyzed using thematic content analysis to identify themes and sub-themes.

    RESULTS: Out of 14 physicians interviewed 11 were aware of PM. They were keen on training to hone their skills and agreed on providing PM. Oncologists believed PM was expensive and given to affluent patients only. Other impeding factors include cost, lack of knowledge, and drug unavailability.

    CONCLUSIONS: Despite basic knowledge and will to practice, resource and cost constraints were marked as significant barriers. Additional training programs and inclusion into the curriculum may help to pave the way to PM implementation in the future. In addition, health authorities and policymakers need to ensure a cheaper PM treatment can be made available for all cancer patients.

    Matched MeSH terms: Precision Medicine
  5. Fulltext A non-printed integrated-circuit textile for wireless theranostics
    Yang Y, Wei X, Zhang N, Zheng J, Chen X, Wen Q, et al.
    Nat Commun, 2021 08 12;12(1):4876.
    PMID: 34385436 DOI: 10.1038/s41467-021-25075-8
    While the printed circuit board (PCB) has been widely considered as the building block of integrated electronics, the world is switching to pursue new ways of merging integrated electronic circuits with textiles to create flexible and wearable devices. Herein, as an alternative for PCB, we described a non-printed integrated-circuit textile (NIT) for biomedical and theranostic application via a weaving method. All the devices are built as fibers or interlaced nodes and woven into a deformable textile integrated circuit. Built on an electrochemical gating principle, the fiber-woven-type transistors exhibit superior bending or stretching robustness, and were woven as a textile logical computing module to distinguish different emergencies. A fiber-type sweat sensor was woven with strain and light sensors fibers for simultaneously monitoring body health and the environment. With a photo-rechargeable energy textile based on a detailed power consumption analysis, the woven circuit textile is completely self-powered and capable of both wireless biomedical monitoring and early warning. The NIT could be used as a 24/7 private AI "nurse" for routine healthcare, diabetes monitoring, or emergencies such as hypoglycemia, metabolic alkalosis, and even COVID-19 patient care, a potential future on-body AI hardware and possibly a forerunner to fabric-like computers.
    Matched MeSH terms: Precision Medicine/instrumentation*; Precision Medicine/methods
  6. Evaluation of production cross-sections for theranostic 67Cu radionuclide via proton-induced nuclear reaction on 68Zn target
    Ali SKI, Khandaker MU, Al-Mugren KS, Latif SA, Bradley DA, Okhunov AA, et al.
    Appl Radiat Isot, 2021 Jul;173:109735.
    PMID: 33915407 DOI: 10.1016/j.apradiso.2021.109735
    Copper-67 (T1/2 = 61.83 h, Eβ-mean=141 keV, Iβ-total=100%; Eγ = 184.577 keV, Iγ = 48.7%) is a promising radionuclide for theranostic applications especially in radio immunotherapy. However, one of the main drawbacks for its application is related to its limited availability. Various nuclear reaction routes investigated in the last years can result in 67Cu production, although the use of proton beams is the method of choice taken into account in this work. The goal of this work is a revision of the cross-sections aimed at 67Cu yield, which were evaluated for the 68Zn(p,2p)67Cu reaction route up to 80 MeV proton energy. A well-defined statistical procedure, i.e., the Simultaneous Evaluation on KALMAN (SOK), combined with the least-squares concept, was used to obtain the evaluated data together with the covariance matrix. The obtained evaluated data were also compared to predictions provided by the nuclear reaction model codes TALYS and EMPIRE, and a partial agreement among them has been found. These data may be useful for both existing and potential applications in nuclear medicine, to achieve an improvement and validation of the various nuclear reaction models, and may also find applications in other fields (e.g., activation analysis and thin layer activation).
    Matched MeSH terms: Precision Medicine
  7. Fulltext Recent Advances in Breast Cancer Diagnosis Entering an Era of Precision Medicine
    Lim, Christopher, Mra, Aung, Chin, Suliong, Venkata Rao, Challa, Aung, Tun, Sieman, Jony, et al.
    Borneo Journal of Medical Sciences, 2019;13(1):3-9.
    MyJurnal
    This article will cover some of the most recent advances in the diagnosis of the world’s most common cancer in women, namely, breast cancer as we enter the era of precision medicine. The authors will discuss the differences between East and West pertaining to the incidence and mortality rates, the types of breast cancer and the revised staging criteria of breast cancer according to the American Joint Committee on Cancer (AJCC) Staging Manual, 8th edition. In addition, the advances of newer imaging modalities are presented and compared with traditional ultrasonography and mammography
    Matched MeSH terms: Precision Medicine
  8. Artificial intelligence and soft skills in radiation oncology: Data versus wisdom
    Boon IS, Lim JS, Yap MH, Au Yong TPT, Boon CS
    J Med Imaging Radiat Sci, 2020 12;51(4S):S114-S115.
    PMID: 32859543 DOI: 10.1016/j.jmir.2020.08.011
    Matched MeSH terms: Precision Medicine
  9. Potential of a sonochemical approach to generate MRI-PPT theranostic agents for breast cancer
    Dheyab MA, Aziz AA, Khaniabadi PM, Jameel MS
    Photodiagnosis Photodyn Ther, 2021 Mar;33:102177.
    PMID: 33429101 DOI: 10.1016/j.pdpdt.2021.102177
    The production of nanomaterials integrating diagnostic and therapeutic roles within one nanoplatform is important for medical applications. Such theranostics nanoplatforms could provide information on imaging, accurate diagnosis and, at the same time, could eradicate cancer cells. Fe3O4@Au core@shell nanoparticles (Fe3O4@AuNPs) have gained broad attention due to their unique innovations in magnetic resonance imaging (MRI) and photothermal therapy (PTT). Seed-mediated growth procedures were used to produce the Fe3O4@AuNPs. In these processes, complicated surface modifications, resulted in unsatisfactory properties. This work used the ability of the sonochemical approach to synthesize highly efficient theranostics agent Fe3O4@AuNPs with a size of approximately 22 nm in 5 min. The inner core of Fe3O4 acts as an MRI agent, whereas the photothermal effect stands accomplished by near-infrared absorption of the gold shell (Au shell), which results in the eradication of cancer cells. We have shown that Fe3O4@AuNPs have great biocompatibility and no major cytotoxicity has been identified. Relaxivity value (r2) of synthesized Fe3O4@Au NPs, measured at 233 mM-1s-1, is significantly higher than those reported previously. The as-synthesized NPs have shown substantial photothermal ablation ability on MCF-7 in vitro under near-infrared laser irradiation. Consequently, Fe3O4@AuNPs synthesized in this study have great potential as an ideal candidate for MR imaging and PTT.
    Matched MeSH terms: Precision Medicine
  10. Fulltext Genes, medicine and society: from paediatrics to genetic counselling and beyond
    Thong MK
    JUMMEC, 2012;15(2):1-8.
    MyJurnal
    The story of clinical genetics is a relatively new one, first spearheaded by paediatrics but increasingly, has taken root in all branches of medicine leading to ‘personalised medicine’. There are expectations that this revolution in genetics will pave the way to genomic medicine and a cure for all inherited disorders. The development of the field of Clinical Genetics and genetic counselling in Malaysia is still in its infancy. Using evidence-based data on genetic disorders such as birth defects, inborn errors of metabolism, genetic syndromes, neurological disorders and hereditary cancers, that hitherto have not been well documented in Malaysia, this review article will focus on findings and issues that will present a unique insight and opportunity to understanding the complex genetic counselling issues related to clinical genetics in Malaysia.
    Matched MeSH terms: Precision Medicine
  11. Attitude, knowledge and ethical perception toward precision medicine among junior and senior medical students: Findings from one Malaysian medical school
    Koh, Kwee Choy, Shanmugan Goonasakaren, Ng, Lam Kean, Chua, Yi Lin, Lee, Jia Ying, Alaric Ding Tian Ang
    International e-Journal of Science, Medicine & Education, 2017;11(3):10-19.
    MyJurnal
    Background: Medical schools are escalating changes
    to meet the need for doctors competent to work in the
    era of precision medicine. Information on the current
    level of awareness of precision medicine among medical
    students can help effect the necessary changes in the
    medical curriculum. A cross-sectional comparative
    study was done to assess the knowledge, attitude and
    perception toward the practice of precision medicine
    among junior and senior medical students in a medical
    school in Malaysia.

    Materials and Method: A survey instrument measuring
    attitude toward precision medicine, perceived
    knowledge of genomic testing concepts, and perception
    toward ethical consideration related to precision
    medicine, was distributed to junior and senior medical
    students. Comparisons were made between senior and
    junior medical students.

    Results: Only about one-third of the 356 respondents
    had heard of precision medicine although 92.7%
    expressed interest to learn more about precision
    medicine. Overall, junior and senior medical students
    had positive attitude toward the adoption of genomeguided
    prescribing and precision medicine but were
    uncomfortable with their knowledge of genomic testing
    concepts. Both junior and senior students were largely
    well grounded in their understanding of ethical issues
    related to precision medicine.

    Conclusions: Knowledge of precision medicine was low
    among junior and senior medical students. Although
    the students supported the use of precision medicine,
    they did not feel adequately prepared to apply genomics
    to clinical practice. Their perceptions on ethical issues
    related to precision medicine were sound. Seniority did
    not appear to influence the perceptions of the students.
    Matched MeSH terms: Precision Medicine
  12. Integrating Patient Concerns into Parkinson's Disease Management
    Lim SY, Tan AH, Fox SH, Evans AH, Low SC
    Curr Neurol Neurosci Rep, 2017 01;17(1):3.
    PMID: 28102483 DOI: 10.1007/s11910-017-0717-2
    Parkinson's disease (PD) is a complex motor and non-motor disorder and management is often challenging. In this review, we explore emerging approaches to improve the care of patients, drawing from the literature regarding patient-centred care, patient and caregiver perspectives and priorities, gaps in knowledge among patients and caregivers and the need for accurate information, individual variability in disease manifestations, prognostication of disease course, new developments in health technologies and personalized medicine, specialty care, pharmacological and non-pharmacological management, financial burden, lifestyle and work-related issues, support groups and palliative care.
    Matched MeSH terms: Precision Medicine
  13. Progress in Clinical Neurosciences, Cognitive Neurosciences, Clinical Psychology, Neurotechnology and Brain Mapping in Malaysia
    Abdullah JM
    Malays J Med Sci, 2021 Apr;28(2):1-14.
    PMID: 33958956 DOI: 10.21315/mjms2021.28.2.1
    Last year, there was an increase in the amount of manpower in Malaysia, especially in terms of the numbers of neurosurgeons, cognitive neuroscientists and clinical psychologists. One way to increase the number of cognitive neurotechnologists in the country in 2021 is to allow neuroscientists to register as neurotechnologists with the Malaysian Board of Technologists (MBOT). The Malaysian Brain Mapping project has risen from its humble beginnings as an initiative of the Universiti Sains Malaysia Brain Mapping Group in 2017. There is currently a proposal for its entry into the national arena via the Precision Medicine Initiative with the Academy Science Malaysia, the Ministry of Science, Technology and Innovation, Ministry of Higher Education and Ministry of Health. The current Malaysian Government's Science, Technology, Innovation and Economy (STIE) plan was launched in 2020, leading to the establishment of neurotechnology as one of 10 STIE drivers.
    Matched MeSH terms: Precision Medicine
  14. Fulltext Natural selection and local adaptation of blood pressure regulation and their perspectives on precision medicine in hypertension
    Hoh BP, Abdul Rahman T, Yusoff K
    Hereditas, 2019;156:1.
    PMID: 30636949 DOI: 10.1186/s41065-019-0080-1
    Prevalence of hypertension (HTN) varies substantially across different populations. HTN is not only common - affecting at least one third of the world's adult population - but is also the most important driver for cardiovascular diseases. Yet up to a third of hypertensive patients are resistant to therapy, contributed by secondary hypertension but more commonly the hitherto inability to precisely predict response to specific antihypertensive agents. Population and individual genomics information could be useful in guiding the selection and predicting the response to treatment - an approach known as precision medicine. However this cannot be achieved without the knowledge of genetic variations that influence blood pressure (BP). A number of evolutionary factors including population demographics and forces of natural selection may be involved. This article explores some ideas on how natural selection influences BP regulation in ethnically and geographically diverse populations that could lead to them being susceptible to HTN. We explore how such evolutionary factors could impact the implementation of precision medicine in HTN. Finally, in order to ensure the success of precision medicine in HTN, we call for more initiatives to understand the genetic architecture within and between diverse populations with ancestry from different parts of the world, and to precisely classify the intermediate phenotypes of HTN.
    Matched MeSH terms: Precision Medicine*
  15. Stage-directed individualized therapy in esophageal cancer
    Goense L, van Rossum PS, Kandioler D, Ruurda JP, Goh KL, Luyer MD, et al.
    Ann N Y Acad Sci, 2016 10;1381(1):50-65.
    PMID: 27384385 DOI: 10.1111/nyas.13113
    Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed.
    Matched MeSH terms: Precision Medicine/methods*
  16. Connecting Proteomics to Next-Generation Sequencing: Proteogenomics and Its Current Applications in Biology
    Low TY, Mohtar MA, Ang MY, Jamal R
    Proteomics, 2019 05;19(10):e1800235.
    PMID: 30431238 DOI: 10.1002/pmic.201800235
    Understanding the relationship between genotypes and phenotypes is essential to disentangle biological mechanisms and to unravel the molecular basis of diseases. Genes and proteins are closely linked in biological systems. However, genomics and proteomics have developed separately into two distinct disciplines whereby crosstalk among scientists from the two domains is limited and this constrains the integration of both fields into a single data modality of useful information. The emerging field of proteogenomics attempts to address this by building bridges between the two disciplines. In this review, how genomics and transcriptomics data in different formats can be utilized to assist proteogenomics application is briefly discussed. Subsequently, a much larger part of this review focuses on proteogenomics research articles that are published in the last five years that answer two important questions. First, how proteogenomics can be applied to tackle biological problems is discussed, covering genome annotation and precision medicine. Second, the latest developments in analytical technologies for data acquisition and the bioinformatics tools to interpret and visualize proteogenomics data are covered.
    Matched MeSH terms: Precision Medicine/trends*
  17. Advancing Global Precision Medicine: An Overview of Genomic Testing and Counseling Services in Malaysia
    Balasopoulou A, Mooy FM, Baker DJ, Mitropoulou C, Skoufas E, Bulgiba A, et al.
    OMICS, 2017 12;21(12):733-740.
    PMID: 29173101 DOI: 10.1089/omi.2017.0136
    Precision medicine, genomic and diagnostic services are no longer limited to developed countries. This broadening in geography of biomarker applications and omics diagnostics also demands empirical study of implementation, diagnostic testing, and counseling practices in the field. For example, the Malaysian population has large ethnic diversity and high prevalence of genetic disorders such as hemoglobinopathies and metabolic disorders. Increased morbidity and mortality from such diseases have a direct impact on society and health system sustainability and for this, decision-making becomes of outmost importance. We report here on our findings on the landscape of genomic testing and genetic counseling services in Malaysia. We first defined the framework of all Malaysian stakeholders that offer genomics services and next, we identified the related information gaps, as depicted through the service providers' online websites. Our research framework revealed that there is a very diverse spectrum of genomics services in Malaysia, in which wet- and dry-laboratory services integrate. Moreover, we identify the current gaps and possible remedies to improve the quality of genomic and predictive analytics, not to mention considerations to ensure robust ethics and responsible innovation. To our knowledge, this is the first such study to be performed for a Southeast Asian country. Our genomics and precision medicine services mapping strategy presented in this study may serve as a model for field assessment at regional, national, and international levels as precision medicine is expanding globally and new governance challenges and opportunities continue to emerge for smart implementation science.
    Matched MeSH terms: Precision Medicine/statistics & numerical data*
  18. Fulltext Towards precision medicine: from quantitative imaging to radiomics
    Acharya UR, Hagiwara Y, Sudarshan VK, Chan WY, Ng KH
    J Zhejiang Univ Sci B, 2018 1 9;19(1):6-24.
    PMID: 29308604 DOI: 10.1631/jzus.B1700260
    Radiology (imaging) and imaging-guided interventions, which provide multi-parametric morphologic and functional information, are playing an increasingly significant role in precision medicine. Radiologists are trained to understand the imaging phenotypes, transcribe those observations (phenotypes) to correlate with underlying diseases and to characterize the images. However, in order to understand and characterize the molecular phenotype (to obtain genomic information) of solid heterogeneous tumours, the advanced sequencing of those tissues using biopsy is required. Thus, radiologists image the tissues from various views and angles in order to have the complete image phenotypes, thereby acquiring a huge amount of data. Deriving meaningful details from all these radiological data becomes challenging and raises the big data issues. Therefore, interest in the application of radiomics has been growing in recent years as it has the potential to provide significant interpretive and predictive information for decision support. Radiomics is a combination of conventional computer-aided diagnosis, deep learning methods, and human skills, and thus can be used for quantitative characterization of tumour phenotypes. This paper discusses the overview of radiomics workflow, the results of various radiomics-based studies conducted using various radiological images such as computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET), the challenges we are facing, and the potential contribution of radiomics towards precision medicine.
    Matched MeSH terms: Precision Medicine/methods*
  19. Proteogenomics: From next-generation sequencing (NGS) and mass spectrometry-based proteomics to precision medicine
    Ang MY, Low TY, Lee PY, Wan Mohamad Nazarie WF, Guryev V, Jamal R
    Clin Chim Acta, 2019 Nov;498:38-46.
    PMID: 31421119 DOI: 10.1016/j.cca.2019.08.010
    One of the best-established area within multi-omics is proteogenomics, whereby the underpinning technologies are next-generation sequencing (NGS) and mass spectrometry (MS). Proteogenomics has contributed significantly to genome (re)-annotation, whereby novel coding sequences (CDS) are identified and confirmed. By incorporating in-silico translated genome variants in protein database, single amino acid variants (SAAV) and splice proteoforms can be identified and quantified at peptide level. The application of proteogenomics in cancer research potentially enables the identification of patient-specific proteoforms, as well as the association of the efficacy or resistance of cancer therapy to different mutations. Here, we discuss how NGS/TGS data are analyzed and incorporated into the proteogenomic framework. These sequence data mainly originate from whole genome sequencing (WGS), whole exome sequencing (WES) and RNA-Seq. We explain two major strategies for sequence analysis i.e., de novo assembly and reads mapping, followed by construction of customized protein databases using such data. Besides, we also elaborate on the procedures of spectrum to peptide sequence matching in proteogenomics, and the relationship between database size on the false discovery rate (FDR). Finally, we discuss the latest development in proteogenomics-assisted precision oncology and also challenges and opportunities in proteogenomics research.
    Matched MeSH terms: Precision Medicine/methods*
  20. Pharmacogenetics of taxanes: impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity
    Jabir RS, Naidu R, Annuar MA, Ho GF, Munisamy M, Stanslas J
    Pharmacogenomics, 2012 Dec;13(16):1979-88.
    PMID: 23215890 DOI: 10.2217/pgs.12.165
    Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic studies of these transporters are expected to provide new approaches for optimizing therapy. Taxanes are approved for the treatment of various cancers. Circulating taxanes are taken up by SLCO1B3 into hepatocytes. The CYP450 enzymes CYP3A4, CYP3A5 and CYP2C8 are responsible for the conversion of taxanes into their metabolites. Ultimately, ABCB1 and ABCC2 will dispose the metabolites into bile canaliculi. Polymorphisms of genes encoding for proteins involved in the transport and clearance of taxanes reduce excretion of the drugs, leading to development of toxicity in patients. This review addresses current knowledge on genetic variations of transporters affecting taxanes pharmacokinetics and toxicity, and provides insights into future direction for personalized medicine.
    Matched MeSH terms: Precision Medicine
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