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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(4): 562-565, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895112

RESUMO

Oral anticoagulants play an important role in the prevention and treatment of thromboembolic diseases.Warfarin,a traditional oral anticoagulant,is limited in clinical use due to its limitations such as narrow therapeutic window and requirements on frequent monitoring and dose adjustment.Direct oral anticoagulants(DOACs)such as dabigatran,rivaroxaban,apixaban,and edoxaban are increasingly used to prevent and treat venous thrombosis or thrombus formation.However,recent studies have documented inter-individual variability in plasma drug levels of DOACs.This article summarizes the recent advances in the pharmacogenomics of DOACs.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial , Farmacogenética , Administração Oral , Fibrilação Atrial/tratamento farmacológico , Dabigatrana , Rivaroxabana
2.
Artigo em Russo | MEDLINE | ID: mdl-32790988

RESUMO

A systematic review of association studies on the role of single nucleotide variants (SNVs) of the dopaminergic system genes on the effectiveness of clozapine in schizophrenia has been perfromed. A search of literature was conducted in PubMed, MedLine, Web of Science Core Collection (Clarivate Analytics), Web of Science, Russian Science Citation Index, Scopus, Scientific Research, Google Scholar, Oxford Press, e-Library from 1995-2019. Association studies of 53 SNPs of genes encoding dopamine receptor isoforms (DRD1), dopamine transporter (SCL6A3) and catechol-O- methyltransferase (COMT), and the nature of their association with the therapeutic response to clozapine were analyzed. The results of SNPs studies of DRD1 and COMT genes are the most controversial. This can be explained by the heterogeneity of the samples and the lack of standardization of methods for evaluating the effectiveness of treatment in the context of association studies. The clear population specificity of the association of some SNPs of DRD1, DRD2 and DRD3 genes with the response to clozapine therapy has been shown. Most of the identified associations are haplotype specific. The obtained regularities of the effect of SNPs of dopaminergic system genes on the effectiveness of clozapine therapy should be considered in an individual approach to treatment of schizophrenia.


Assuntos
Clozapina , Esquizofrenia , Catecol O-Metiltransferase/genética , Dopamina , Genótipo , Humanos , Farmacogenética , Polimorfismo de Nucleotídeo Único , Federação Russa
3.
Rev Lat Am Enfermagem ; 28: e3265, 2020.
Artigo em Português, Espanhol, Inglês | MEDLINE | ID: mdl-32813781

RESUMO

OBJECTIVE: to verify the existence of elements that justify the use of pharmacogenetics by the Brazilian nurse. METHOD: this is a quantitative, cross-sectional, observational, descriptive study, whose final sample was 67 individuals. The participants were healthy at the time of the study and reported a history of previous use and the occurrence of adverse effects by drugs commonly used and metabolized by CYP2C9. We collected 4 mL of venous blood for subsequent DNA extraction by salting out method and genotyping of the CYP2C9*2 and CYP2C9*3 polymorphisms, using Polymerase Chain Reaction in real time using Taqman assays. RESULTS: the use of drugs metabolized by CYP2C9 was frequent (more than 75% of the individuals have already used between 2 or 4 of these drugs). Regarding adverse events, there were 19 perceived symptomatic occurrences associated with drugs metabolized by CYP2C9. The allele frequency of the polymorphism * 2 and * 3 in the population studied was 11.1% and 7.5%, respectively, and there was a coincidence between the presence of alleles of low enzyme activity and the occurrence of adverse effects. CONCLUSION: there are elements that justify the adoption of pharmacogenetics in the nursing care to reduce the occurrence of adverse reactions to drugs metabolized by CYP2C9.


Assuntos
Hidrocarboneto de Aril Hidroxilases , Farmacogenética , Brasil , Estudos Transversais , Citocromo P-450 CYP2C9/genética , Empoderamento , Humanos
4.
Georgian Med News ; (302): 63-68, 2020 May.
Artigo em Russo | MEDLINE | ID: mdl-32672692

RESUMO

This article reviews data for pharmacogenetics findings for treatment for chronic heart insufficiency of heart failure. Also, it discusses connections of genetic polymorphism with a risk of developing heart failure and how it affects the choice of a treatments medicine. The article investigates genetically determined factors of the risk of developing glycoside toxicity. One of the causes is polymorphism of the MDR1 gene encoding glycoprotein P, a transporter, that is involved in the absorption of drugs in the intestines and excretion by the kidneys. Also, the genetic characteristics of ACE in patients with heart failure are discussed. The data is presented from the study of the role of genetic liver metabolism polymorphism regarding efficacy and safety of loop diuretic torasemide. Data for genetic polymorphism of the metabolism of the main beta blocker, used in chronic heart failure metoprolosuccinate is also discussed. Data for roll ß1-AP polymorphism in the clinical use of ß-AB in patients with heart failure. Further observations are needed from longer studies, that will evaluate long-term efficacy and safety outcomes for medicines related to genetic traits.


Assuntos
Insuficiência Cardíaca , Farmacogenética , Antagonistas Adrenérgicos beta , Diuréticos , Humanos , Torasemida
5.
Stud Health Technol Inform ; 272: 47-50, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604597

RESUMO

IT providers offering services based on genetic data face serious challenges in managing health data in compliance with the General Data Protection Regulation (GDPR). Based on a literature research and our experiences, an overview of GDPR compliant processing of sensitive data is given. The GDPR requirements for processing sensitive data were specified for a use case concerning a service provider of a pharmacogenomic decision support system. Start-ups who want to enter into the health market also have to comply with the Medical Device Regulation (MDR). The associated efforts for legal compliance constitute an impediment for many start-ups. We created a comprehensive overview, which aligned the requirements of the GDPR with the life-cycle of a medical device. This overview shall help start-ups to grasp and overcome the regulatory hurdles faster.


Assuntos
Farmacogenética , Segurança Computacional
6.
Stud Health Technol Inform ; 272: 195-198, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604634

RESUMO

The goal of this study was to evaluate association between number of pharmacogenetic variants and length of hospital stay. Electronic medical records were combined with exome sequencing results in 450 hospitalized patients. De-identified data set was used to characterize urgent care utilization and to identify presence of 44 actionable pharmacogenetic variants according to the guidelines of the Clinical Pharmacogenetics Implementation Consortium. The average age was 58.03 ± 16.47 ranging from 20 to 91 years old, average number of pharmacogenetic variants was 61.22 ± 26.52 ranging from 20 to 169, and mean length of hospital stay was 6.50 ± 4.29 ranging between 1 and 42 days. After adjusting for patient socio-demographics and overall disease severity reflected by the Charlson comorbidity index, a significant association between mean length of stay and number of pharmacogenetic variants was found using generalized linear regression (p-value < 2.2e-16).


Assuntos
Variantes Farmacogenômicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Registros Eletrônicos de Saúde , Humanos , Tempo de Internação , Modelos Lineares , Pessoa de Meia-Idade , Farmacogenética , Adulto Jovem
8.
Stud Health Technol Inform ; 270: 267-271, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32570388

RESUMO

Information relevant to pharmacogenomics studies is available in several open databases, which makes it difficult to synthetize the available data. Within the PractikPharma project, several databases were integrated to PGxLOD, a resource dedicated to the generation and verification of pharmacogenomic influence on drug responses. The Comparative Toxicogenomic Database (CTD) describes the toxic effects of many chemicals on living species based on the literature. Since drugs are peculiar chemicals and side effects are peculiar toxic effects, we aimed at extracting information from CTD that matches drug side effects in the human specie.


Assuntos
Doença/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Substâncias Perigosas/toxicidade , Farmacogenética , Toxicogenética , Bases de Dados Factuais , Doença/genética , Humanos , Pesquisa , Integração de Sistemas
9.
Pharmacogenomics ; 21(10): 695-703, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32501190

RESUMO

COVID-19 utilizes the ACE2 pathway as a means of infection. Early data on COVID-19 suggest heterogeneity in the severity of symptoms during transmission and infection ranging from no symptoms to death. The source of this heterogeneity is likely multifaceted and may have a genetic component. Demographic and clinical comorbidities associated with the severity of infection suggest that possible variants known to influence the renin-angiotensin-aldosterone (RAAS) system pathway (particularly those that influence ACE2) may contribute to the heterogenous infection response. ACE2 and Ang(1-7) (the product of ACE2) seem to have a protective effect on the pulmonary and cardiac systems. Hypertension medication modulation, may alter ACE2 and Ang(1-7), particularly in variants that have been shown to influence RAAS system function, which could be clinically useful in patients with COVID-19.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Peptidil Dipeptidase A/efeitos dos fármacos , Peptidil Dipeptidase A/genética , Farmacogenética , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/genética , Humanos , Pandemias , Testes Farmacogenômicos , Sistema Renina-Angiotensina/efeitos dos fármacos
10.
Stud Health Technol Inform ; 270: 618-622, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32570457

RESUMO

Pharmacogenetic testing can prevent adverse drug events but has rarely found its way into clinical routine. One reason is the lack of tools for smooth and automatable integration of pharmacogenetic knowledge into existing processes. Especially, electronic medical records (EMR) represent a suitable environment for such tools. We developed a modular service-oriented prototype of a pharmacogenetic decision support system within an EMR system of the Bern University Hospital. Here, we present the component architecture of our system and discuss issues required for generalizing our results.


Assuntos
Testes Farmacogenômicos , Sistemas de Apoio a Decisões Clínicas , Registros Eletrônicos de Saúde , Farmacogenética , Software
11.
Croat Med J ; 61(2): 147-158, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32378381

RESUMO

Older people are increasingly susceptible to adverse drug reactions (ADRs) or therapeutic failure. This could be mediated by considerable polypharmacy, which increases the possibility of drug-drug and drug-gene interactions. Precision medicine, based on individual genetic variations, enables the screening of patients at risk for ADRs and the implementation of personalized treatment regimens. It combines genetic and genomic data with environmental and clinical factors in order to tailor prevention and disease-management strategies, including pharmacotherapy. The identification of genetic factors that influence drug absorption, distribution, metabolism, excretion, and action at the drug target level allows individualized therapy. Positive pharmacogenomic findings have been reported for the majority of cardiovascular drugs (CVD), suggesting that pre-emptive testing can improve efficacy and minimize the toxicity risk. Gene variants related to drug metabolism and transport variability or pharmacodynamics of major CVD have been translated into dosing recommendations. Pharmacogenetics consortia have issued guidelines for oral anticoagulants, antiplatelet agents, statins, and some beta-blockers. Since the majority of pharmacogenetics recommendations are based on the assessment of single drug-gene interactions, it is imperative to develop tools for the prediction of multiple drug-drug-gene interactions, which are common in the elderly with comorbidity. The availability of genomic testing has grown, but its clinical application is still insufficient.


Assuntos
Doenças Cardiovasculares , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Farmacogenética , Idoso , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Humanos , Medicina de Precisão
12.
Yakugaku Zasshi ; 140(5): 673-675, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32378671

RESUMO

Since September of 2017, the Department of Pharmacy at Keio University Hospital has participated in activities of the A-3 Group in the "Program for Promoting a Platform of Genomics-based Drug Discovery" conducted by the Japan Agency for Medical Research and Development (AMED). The A-3 Group works to develop programs for fostering human resources in genomic medicine in order to solve various problems, and the Keio Department of Pharmacy plans and holds twice-yearly seminars for pharmacists interested in genomic medicine. In this review, we give an overview of efforts toward the development of pharmacists involved in genomic medicine, and we present the results of questionnaires about previous seminars.


Assuntos
Educação em Farmácia/métodos , Terapia Genética , Genômica/educação , Farmacêuticos , Farmacogenética/educação , Humanos , Japão , Inquéritos e Questionários
13.
Clin Drug Investig ; 40(7): 617-628, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32415468

RESUMO

BACKGROUND: Validated genomic biomarkers for oncological drugs are expanding to improve targeted therapies. Pharmacogenetics research focusing on the mechanisms underlying imatinib suboptimal response might help to explain the different treatment outcomes and drug safety profiles. OBJECTIVE: To investigate whether polymorphisms in genes encoding cytochrome P450 (CYP) enzymes and ABCB1 transporter affect imatinib pharmacokinetic parameters. METHODS: A prospective, multicenter, pharmacogenetic pilot study was performed in the context of two separate oral imatinib bioequivalence clinical trials, which included 26 healthy volunteers. DNA was extracted in order to analyze polymorphisms in genes CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and ABCB1. Imatinib plasma concentrations were measured by HPLC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods using WinNonlin software. RESULTS: Volunteers (n = 26; aged 24 ± 3 years; 69% male) presented regular pharmacokinetic imatinib data (concentration at 24 h, 436 ± 140 ng/mL and at 72 h, 40 ± 26 ng/mL; AUC0-72 32,868 ± 10,713 ng/mL⋅h; and Cmax 2074 ± 604 ng/mL). CYP2B6 516GT carriers showed a significant reduction of imatinib concentration at 24 h (23%, 391 ng/dL vs 511 ng/dL in 516GG carriers, p = 0.005) and elimination half-life (11%, 12.6 h vs 14.1 h in 516GG carriers, p = 0.041). Carriers for CYP3A4 (*22/*22, *1/*20 and *1/*22 variants) showed a reduced frequency of adverse events compared to *1/*1 carriers (0 vs 64%, p = 0.033). The other polymorphisms analyzed did not influence pharmacokinetics or drug toxicity. CONCLUSION: CYP2B6 G516T and CYP3A4 *20,*22 polymorphisms could influence imatinib plasma concentrations and safety profile, after single-dose administration to healthy subjects. This finding needs to be confirmed before it is implemented in clinical practice in oncological patients under treatment with imatinib.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Mesilato de Imatinib/farmacocinética , Polimorfismo Genético , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Feminino , Voluntários Saudáveis , Humanos , Mesilato de Imatinib/administração & dosagem , Masculino , Farmacogenética , Projetos Piloto , Estudos Prospectivos , Adulto Jovem
14.
PLoS One ; 15(5): e0233316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428022

RESUMO

Oral anticoagulant (OAC) therapy has been the main treatment approach for stroke prevention for decades. Warfarin is the most widely prescribed OAC in the United States, but is difficult to manage due to variability in dose requirements across individuals. Pharmacogenomics may mitigate risk concerns related to warfarin use by fostering the opportunity to facilitate individualized medicine approaches to warfarin treatment (e.g., genome-guided dosing). While various economic evaluations exist examining the cost-effectiveness of pharmacogenomics testing for warfarin, few observational studies exist to support these studies, with even fewer using genotype as the main exposure of interest. We examined a cohort of individuals initiating warfarin therapy between 2004 and 2017 and examined bleeding and cost outcomes for the year following initiation using Mayo Clinic's billing and administrative data, as well the Mayo Clinic Rochester Cost Data Warehouse. Analyses included descriptive summaries, comparison of characteristics across exposure groups, reporting of crude outcomes, and multivariate analyses. We included N = 1,143 patients for analyses. Just over a third of our study population (34.9%) carried a warfarin-sensitive phenotype. Sensitive individuals differed in their baseline characteristics by being of older age and having a higher number of comorbid conditions; myocardial infarction, diabetes, and cancer in particular. The occurrence of bleeding events was not significantly different across exposure groups. No significant differences across exposure groups existed in either the likelihood of incurring all-cause healthcare costs or in the magnitude of those costs. Warfarin-sensitive individuals were no more likely to utilize cardiovascular-related healthcare services; however, they had lower total and inpatient cardiovascular-related costs compared to warfarin-insensitive patients. No significant differences existed in any other categories of costs. We found limited evidence that warfarin-sensitive individuals have different healthcare spending than warfarin-insensitive individuals. Additional real-world studies are needed to support the traditional economic evaluations currently existing in the literature.


Assuntos
Farmacogenética/métodos , Varfarina/economia , Varfarina/uso terapêutico , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Biomarcadores Farmacológicos/análise , Biomarcadores Farmacológicos/sangue , Estudos de Coortes , Análise Custo-Benefício , Citocromo P-450 CYP2C9/genética , Assistência à Saúde , Feminino , Genômica , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Medicina de Precisão/métodos , Acidente Vascular Cerebral/epidemiologia , Estados Unidos , Vitamina K Epóxido Redutases/genética , Varfarina/metabolismo
15.
PLoS One ; 15(5): e0230950, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365122

RESUMO

A pharmacogenomics-based pathway represents a series of reactions that occur between drugs and genes in the human body after drug administration. PG-path is a pharmacogenomics-based pathway that standardizes and visualizes the components (nodes) and actions (edges) involved in pharmacokinetic and pharmacodynamic processes. It provides an intuitive understanding of the drug response in the human body. A pharmacokinetic pathway visualizes the absorption, distribution, metabolism, and excretion (ADME) at the systemic level, and a pharmacodynamic pathway shows the action of the drug in the target cell at the cellular-molecular level. The genes in the pathway are displayed in locations similar to those inside the body. PG-path allows personalized pathways to be created by annotating each gene with the overall impact degree of deleterious variants in the gene. These personalized pathways play a role in assisting tailored individual prescriptions by predicting changes in the drug concentration in the plasma. PG-path also supports counseling for personalized drug therapy by providing visualization and documentation.


Assuntos
Biologia Computacional/métodos , Redes e Vias Metabólicas/genética , Preparações Farmacêuticas/metabolismo , Farmacogenética/métodos , Medicina de Precisão/métodos , Software , Bases de Dados Genéticas , Tratamento Farmacológico/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Absorção Gastrointestinal/genética , Estudos de Associação Genética , Humanos , Inativação Metabólica/efeitos dos fármacos , Inativação Metabólica/genética , Armazenamento e Recuperação da Informação/métodos , Redes e Vias Metabólicas/efeitos dos fármacos , Modelos Teóricos
18.
Crit Rev Oncol Hematol ; 149: 102939, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32259776

RESUMO

A substantial proportion of cancer patients experience chemotherapy-induced nausea and vomiting (CINV) despite the use of antiemetic drugs. Prevalent genetic polymorphisms involved in antiemetic drug metabolism, drug transport and receptor pathways likely affect the effectiveness of antiemetics. Knowledge on which polymorphisms to integrate into individualised clinical care is needed. We did a systematic review evaluating the association between polymorphisms and effectiveness of antiemetics in cancer patients receiving moderately to highly emetogenic chemotherapy. Twenty studies n = 2331 evaluated eight polymorphisms in five candidate genes involved in 5-HT3 antagonist pathways. HTR3C C1214G increased the risk of acute chemotherapy-induced vomiting in the dominant model (odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.08-6.63). ABCB1 C3435T reduced the risk of acute CINV in the recessive model (OR = 0.60, 95 % CI: 0.44-0.81). Future studies should evaluate candidate genes that affect pharmacogenetics of other antiemetics beside 5-HT3 antagonists.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Sistema Enzimático do Citocromo P-450 , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Farmacogenética , Receptores 5-HT3 de Serotonina , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Vômito/prevenção & controle , Antineoplásicos/uso terapêutico , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/genética , Humanos , Náusea/induzido quimicamente , Náusea/genética , Polimorfismo Genético/genética , Receptores 5-HT3 de Serotonina/efeitos dos fármacos , Receptores 5-HT3 de Serotonina/genética , Vômito/induzido quimicamente , Vômito/genética
19.
Thorac Surg Clin ; 30(2): 121-125, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32327170

RESUMO

Almost a half of patients diagnosed with nonesmall-cell lung cancer (NSCLC) present with incurable disease, and a significant number of patients who are treated with curative intent for early-stage disease will eventually recur. Systemic therapy is selected based on tumor histology, squamous versus nonsquamous NSCLC, molecular testing, and PD-L1 score. Depending on PD-L1 score, patients are eligible for immunotherapy alone or in combination with chemotherapy in the first-line setting. Oncogenic driver mutations can be detected in approximately 50% of patients with nonsquamous NSCLC of which several can be targeted therapeutically with small molecular inhibitors. Continued research is needed for more specific agents with less toxicity and better central nervous system penetration, and agents to treat patients who develop resistance against targeted treatments and immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia de Alvo Molecular , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Farmacogenética , Medicina de Precisão/métodos , Medicina de Precisão/tendências
20.
Thorac Surg Clin ; 30(2): 147-156, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32327173

RESUMO

ROS1-rearranged non-small cell lung cancer (NSCLC) makes up approximately 1% to 2% of all NSCLC, is oncogenically driven by a constitutively activated ROS1 kinase paired with certain fusion partners, and can be detected by several different assays. These patients are initially treated with tyrosine kinase inhibitors (TKIs), which target the activated ROS1 kinase. Eventually these tumors develop resistance to initial TKI treatment through secondary kinase mutations that block TKI binding or activation of bypass signaling pathways, which subvert ROS1 as the driver of the malignancy. Investigation of several TKIs that have shown efficacy in secondary resistant patients is underway.


Assuntos
Neoplasias Pulmonares , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Farmacogenética , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética
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