Iuphar.us

Latin American Pharmacogenomics and Personalized MedicineConference 2nd Latin American Pharmacogenomics and Personalized Medicine Congress
27–29 June 2012, Rio de Janeiro, RJ, Brazil
There are nearly 600 million people living in 24 Latin American countries, speaking two major languages (Portuguese and Spanish) and sharing ancestral roots in America, Europe and Africa. Ethnic and cultural diversity, socioeconomical, scientific and technological disparities across Latin America must be taken into account in the design, interpretation and implications of pharmacogenomic studies in this region. The conference covered some of these aspects, but also took on a more global approach on the growing contribution of genomic information and biotechnological tools to the way medicines are developed, regulated and prescribed to patients. Translation of pharmacogenomics into clinical practice was the topic of a keynote lecture and two debate sessions. A preconference Introductory Course of Pharmacogenomics was offered.
The 2nd Latin American Pharmacogenomics the chronic nature of psychiatric disorders Guilherme Suarez-Kurtz
and Personalized Medicine Congress, and the common occurrence of comor- Division of Pharmacology, Instituto Nacional de Câncer,
attended by a broad audience of nearly 200 bidities) as well as drug-related factors Rio de Janeiro, Brazil
Tel.: +55 21 3207 6502 participants, mostly from Brazil, but also (i.e., active drug metabolites and the lack Fax: +55 21 3207 6542 Argentina, Chile, Colombia, Costa Rica, of well defined pharmacokinetic–phar- [email protected]Cuba, Ecuador and Mexico, opened with a macodynamic relationships). The second presentation by Julie A Johnson (University debate, chaired by LLerena, covered clopi-of Miami, FL, USA) on ‘Translating phar- dogrel and warfarin. The high levels of macogenomics to clinical practice', in evidence for the association between geno-which the goals and achievements of the type and dose (warfarin) or drug response Pharmacogenomics Research Network (clopidogrel) were reviewed by Johnson, (PGRN) [101], Clinical Pharmacogenetics who coauthored the CPIC guidelines Implementation Consortium (CPIC) [102] for both drugs. Guilherme Suarez-Kurtz and Pharmacogenomics Knowledge Base (Instituto Nacional do Câncer, RJ, Brazil) (PharmGKB) [103] were reviewed. CPIC, discussed the performance of warfarin dos-one of the consortia that has arisen from ing algorithms across populations, with an the PGRN, evaluates the evidence for emphasis on the differential distribution clinical implementation of pharmacoge- of the relevant polymorphisms in CYP2C9 netics and provides guidelines for using and VKORC1, and the controversial use of genetic information in drug prescription; ethnic/racial labels that do not encompass to date, six guidelines have been published. human diversity worldwide.
PharmGKB is a valuable web-based infor- A symposium on ‘New Tools and mation source for pharmacogenomics, with Technologies in Pharmacogenomics content ranging from basic information on Research' was chaired by Karen Weck SNPs and genes to clinical annotations for (University of North Carolina, NC, USA), pharmacogenomics. The clinical adoption who initially reviewed the required ana-of pharmacogenomics-informed prescrip- lytical attributes of pharmacogenomic tion was further discussed in two debate tests, the impact of differential prevalence sessions, the first of which focused on psy- of pharmacogenetic polymorphisms across chiatry and was chaired by Mauricio Silva ethnic groups, and postanalytic factors de Lima (Roche, SP, Brazil). The discus- such as clinical validity and clinical util- sants, Mara Hutz (Universidade Federal do ity. Weck then discussed the advantages Rio Grande do Sul, RS, Brazil) and Adrian and challenges associated with the advent LLerena (Universidad de Extremadura, of multiplexed microarray technolo-Extremadura, Spain), agreed that appli- gies and newer next-generation sequenc- cation of pharmacogenetics into clinical ing platforms. The rapid pace at which psychiatry practice holds great promise, these technologies continue to move at but is hindered by clinical (i.e., diagnostic Ion Torrent at Life Technologies (CA, uncertainty, heterogeneous presentation, USA), was highlighted by Pat Brooks (Ion 10.2217/PGS.12.128 2012 Future Medicine Ltd Pharmacogenomics (2012) 13(13), 1449–1452 & Vewsw – Conference Scene Torrent), who introduced new products mechanistic drug development translated such as the Proton™ instrument, to be in many FDA-approved new molecular launched later this year, and the Proton I entities in 2011 having a pharmacog-and Proton II chips.
enomic component as part of the devel- Issam Zineh (US FDA, MD, USA) opment program. Zineh concluded by chaired the second symposium, entitled offering a perspective on the next 10 years. ‘Personalized Medicine: Across the Drug He focused on enhanced intercenter com-Development, Utilization and Regulation munication at the FDA, the development Continuum'. José Fernando Perez (Recepta of guides to industry relevant to personal-Biopharma, SP, Brazil) described the devel- ized medicine drug development and the opment by Recepta Biopharma of a mono- importance of considering novel applica- clonal antibody for the treatment of ovarian tions for pharmacogenomics in the context cancer that has recently received approval of globalized drug development.
for clinical trials from both the FDA and In his keynote lecture, entitled Anvisa (Brasilia, Brazil), the Brazilian ‘Pharmaco genomic and Pharmaco-drug regulatory agency. Frank Scappaticci epigenomic Biomarkers for Drug Therapy', (Genentech/Roche, CA, USA) described Magnus Ingelman-Sundberg (Karolinska two types of innovation in biologics that Institutet, Stockholm, Sweden) initially Roche is undertaking: the first exemplified described the importance of adverse drug by a new antibody–drug conjugate agent reactions in the clinical setting and the that is showing promise in Her2-positive prevention of such reactions by utilizing metastatic breast cancer and the second validated pharmacogenomics biomark-related to the development of surrogate end ers. This was followed by excellent over-points for clinical oncology trials, such as views of the role of DNA methylation and minimal residual disease for chronic lym- 5-hydroxymethylation for the control of phocytic leukemia and pathologic com- gene expression and the development of plete response rate in neoadjuvant breast epigenetic drugs, particularly for cancer cancer. George Patrinos (University of treatment. Ingelman-Sundberg concluded Patras, Patras, Greece) reported the activi- his talk with a vision of the use of phar- ties of the European Regional Center of macogenomic and pharmacoepigenomic the Pharmacogenomics for Every Nation markers, where labeling of specific drugs Initiative (PGENI) [104], and the Golden for pharmacogenetic testing provides a Helix Institute of Biomedical Research useful instrument for a more effective and [105], including recruitment of DNA sam- safer drug therapy in the future.
ples from healthy volunteers, organization The symposium on ‘Pharmacogenomics of education activities, surveying the phar- in Oncology', chaired by Howard macogenomic environment in European McLeod (University of North Carolina) developing countries and the establish- started with Alfredo Hidalgo-Miranda ment of guidelines and recommendations (National Institute of Genomic Medicine, for integrating pharmacogenomics in DF, Mexico) presenting results of the these countries' healthcare systems. The Slim Initiative of Genomic Medicine last two talks in the symposium dealt with (SIGMA) project of characterization of drug regulatory issues. Marcelo Moreira, the genomic basis of different cancer from the Anvisa [106], went on to review types. Whole-exome sequencing identi-the drug regulatory legislation in Brazil, fied loss-of-function mutations in the with an emphasis on its impact in phar- NOTCH family of genes in head and neck macogenomics research. In his talk ‘On tumors, and mutations and deletions of a Decade of Personalized Medicine at the CBFB transcription factor in breast the US FDA', Zineh argued that person- tumors. In 7% of triple-negative breast alized medicine has represented an area tumors, somatic translocation involving of progression at the FDA over the past MAGI3 and AKT3 leading to constitu-10 years, evident in initiatives such as the tive phosphorylation activity and cellular Critical Path Initiative, the Critical Path transformation was detected. Notably, Opportunities List and the most recent the activity of the fusion protein could Advancing Regulatory Science Initiative. be abrogated by a small-molecule inhibi-The use of pharmacogenomics to enhance tor of AKT, which might prove to be of Pharmacogenomics (2012) 13(13)
future science group Conference Scene – News & Views therapeutic value. Scappaticci offered an [107], a consortium of 18 research groups, overview of key issues and challenges in with the mission to provide leadership in the development of biologics including pharmacogenomic research and educa-biosimilars, highlighting the complexity tion in Brazil, with an impact on popu-of biologic protein drugs and manufac- lation health. Results from a Refargen turing challenges. The recently released study on the influence of bio geographical FDA guidelines for biosimilar agents were ancestry on the frequency distribution discussed and a case example of two anti- of 60 pharmacogenetic polymorphisms CD20 targeted biologics showing different in Brazilians showed that: first, the fre-safety profiles after Phase III trials were quency distribution of polymorphisms var-completed was provided, to emphasize ies across geographical regions and within the need for rigorous clinical studies to self-reported color categories and second, ensure the safety of any new biologics. that ‘racial/ethnic/color' categories do In the following talk, entitled ‘Discovery not capture the diversity of the Brazilian is necessary, but not sufficient' (to fulfil population, which must be dealt with as a the pharmaco genomics' promise of indi- continuous variable. LLerena went on to vidualized drug therapy), McLeod argued describe the Iberian American Network of that, after finding the ‘right' biomarkers Pharmacogenetics and Pharmacogenomics and validating them in robust data sets, (Ribef) [108], a consortium of researchers it is imperative to apply this knowledge in in 16 Latin American countries, Spain the clinical setting. Examples were pro- and Portugal and the Consorcio Europeo vided of clinically relevant associations e IberoAmericano de Farmacogenética de of pharmacogenetic polymorphisms with Poblaciones (CEIBA). Studies from both the efficacy and toxicity of cancer drugs, consortia have so far focused mainly on including CYP2C8*3 and paclitaxel- genotyping CYP2D6 genetic polymor-induced neuropathy, CYP2D6 phenotype phisms and measuring the metabolic and relapse-free survival in breast cancer, ratios of CYP phenotype probes (i.e., dex-and the influence of the TSER genotype tromethorphan, debrisoquine, losartan, on the proportion of complete response to caffeine and omeprazol) in various Latin chemoradiation (5-fluorouracil based) of American populations.
rectal tumors.
Matthias Schwab (Institute of Clinical Hutz chaired a symposium dedi- Pharmacology, Stuttgart, Germany) cated to ‘Pharmacogenomics in Latin chaired the symposium on ‘Recent America'. Jorge Duconge (University of Progress in the Pharmacogenomics of Puerto Rico, PR, USA) presented a phys- Drug Transporters'. Genetic control of iogenomic analysis of the Puerto Rican ABC transporter expression was dis-population ancestry and described a cussed by Deanna Kroetz (University of pharmacogenetic-driven warfarin dosing California San Francisco, CA, USA). A algorithm. A distinct feature of this algo- specific example with ABCG2 detailed the rithm is an admixture vector component, combined bioinformatic and experimental which, per se, accounted for 5.7% of the approaches to identify enhancer regions warfarin dose variance in Puerto Rican that control the expression of ABCG2 in patients, and for 67% of this variance the human liver and kidney. This gene-when combined with five other covariates. centric analysis was in contrast to a fam-Hidalgo-Miranda presented data from ily-wide expression quantitative trait loci the PGENI Mexican Regional Center on analysis of ABC transporter expression the distribution of 1936 polymorphisms in the human kidney. The long-term goal in 225 pharmacogenes, among different of these studies is to assemble a panel of Mexican, including Amerindian groups, SNPs that can be considered markers of and argued that differences in allele distri- variable drug response and toxicity. Ingolf bution across the groups will be valuable Cascorbi (Christian Albrechts University, to inform public health decisions regard- Kiel, Germany) discussed recent evidence ing specific drug use in Mexico. The next from his group showing that deregulated two talks dealt with pharmacogenomic miRNA expression patterns of tumor cells networks in Latin America. Suarez-Kurtz may interfere with drug response. In one introduced the Brazilian network Refargen study, downregulation of certain miRNAs future science group News & Views – Conference Scene abolished imatinib resistance of BCR/ABL- pharmacogenomic polymorphisms among overexpressing K-562 cells through upregu- PGENI countries and discussed the use of lation of ABCG2. In another study, induc- these data for medication prioritization for tion of ABCC2 protein by rifampicin was individual countries and to identify popu-counteracted by miRNA 379 in HepG2 lation subgroups at higher risk of toxicity cells, an observation that might contrib- and treatment failure. Importantly, PGENI ute towards explaining the discrepancies provides support for building local infra-between mRNA and protein expression structure in the participating countries for following external stimuli though PXR lig- future pharmacogenetic research studies. ands. Schwab focused on the influence of McLeod emphasized that modern medical DNA methylation on interindividual dif- therapy is a key component of improved ferences in drug response, best studied in healt, that requires integration into clinical cancer patients. Tissue-specific DNA meth- practice and into public health policy to be ylation alters the expression of pharmacoki- netic genes encoding CYP450 enzymes as Abstracts of the oral presentations and well as drug transporters. As an example, posters are available at the Refargen web-
DNA methylation of the hepatic SLC22A1 site [107]. At the closing ceremony, it was
(OCT1) uptake transporter was shown announced that the 3rd Latin American
to be associated with downregulation of Pharmacogenomics and Personalized
SLC22A1 in hepatocellular carcinoma, Medicine will be held in Mexico, in 2014.
which might be a novel biomarker for diag-
nosis and prognosis as well as a target for Financial & competing interests
demethylating agents such as decitabine for disclosure
therapy of hepatocellular carcinoma.
The author has no relevant affiliations or financial In his keynote lecture entitled ‘Turning involvement with any organization or entity with a Genetic Diversity into Rational Drug financial interest in or financial conflict with the Policy', McLeod presented the rationale, subject matter or materials disclosed in the manu-purposes, organization and achievements script apart from those disclosed. This includes of PGENI, a worldwide consortium that employment, consultancies, honoraria, stock owner-comprises two regional centers in Latin ship or options, expert testimony, grants or patents America (Rio de Janeiro, Brazil and received or pending, or royalties.
Mexico City, Mexico). McLeod showed No writing assistance was utilized in the results for the differential distribution of production of this manuscript. 104 Pharmacogeneomics for Every Nation 107 Brazilian Pharmacogenomics Netwrok 101 The Pharmacogenomics Research Network. 105 The Golden Helix Institute of Biomedical 108 Iberian American Pharmacogenetics and 102 CPIC: Clinical Pharmacogenetics Pharmacogenomics Network. Implementation Consortium. 106 Brazilian National Health Surveillance 103 PharmGKB: Pharmacogenomics Knowledge Agency (Anvisa). Pharmacogenomics (2012) 13(13)
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Source: http://www.iuphar.us/files/PGx/Suarez-Kurtz_2012_Pgenomics_LAPGx.pdf