un studiu pt ggenetica la ubb cluj copiat din pdf

8/9/2019 un studiu pt ggenetica la ubb cluj copiat din pdf

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Editorialinsights into genetic variation and molecular mechanisms underlying humandiversity have improved our understanding of the complexity of life anddisease heterogeneity.

Christos KatsiosDepartment of Surgery, IoanninaUniversity School of Medicine,Ioannina, !""# $reece

Dimitrios H Roukos%uthor for correspondence&'ersonali(e )ancer Medicine, *io+an,Department of Surgery, IoanninaUniversity School of Medicine,Ioannina, !""#, $reece-el.& /# 01! "## 20/3ax& /# 01! "## 2#4drouos5uoi.gr

Individual genomes and personalized

medicine:life diversity and complexityPatients and tumors are unique. The conceptualdesign is great. Identifying the genetic variantsunderlying phenotype can lead to personalizedmedicine. Tailoring the best medical interventionto the right individual or patient can dramaticallyimprove health. A decade after the rstdraft of human genome sequence !"#$% and thepromises of a health revolution# &hat progresshas been made in both genomics and personalized

medical practice and &hat are the challengesand perspectives to deal &ith for the next decade'The use of personalized medicine to improveboth the prevention and cure of disease is potentiallyachievable through: predicting both thedisease ris( among healthly individuals in thegeneral population and the therapeutic responseamong patients. )enomic information fromindividuals or patients can substantially contributeto biomar(er*based guided personalizedprevention and treatment.

The rst strategy to use personalized medicine#in the prevention setting# involves identifyinghigh*ris( individuals that may developma+or common diseases# such as cardiovasculardisorder# diabetes and cancer# and then selectingthe most appropriate preventive intervention toprotect them from these diseases. This strategycan substantially reduce disease incidence and itis particularly important for hard*to*treat disorders#such as cancer. ,o&ever# despite currentresearch e-orts# the development of robust biomar(ersbased on primary prevention has only


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modestly improved.In the second strategy# in the treatment setting#e-orts by academia and industry havebeen focused on ho& to improve diagnosticsand prognosis of diseases and ho through thedevelopment of predictors of drug response and

adverse e-ects# to improve the safety and ecacyof drugs. Indeed# not only is the therapeuticresponse rate for several complex diseases lobut general toxicity rates of currently used agentsare also still alarmingly high./everal research strategies and scienticelds have been developed to&ards personalizedmedicine. Pharmacogenetics# studying thegenetic associations &ith drug ecacy and toxicityhas led to the identication of several dugmetabolizingenzymes# &ith the most importantbelonging to the cytochrome P012 family !3%.

The aim is to predict adverse e-ects to guideindividualized treatment. 4espite overlap &ithpharmacogenetics# the term pharmacogenomicsis distinct because it evaluates the application ofgenomics to drug discovery. Pharmacogenomicsinvolves the mechanism of the action of drugson cells as revealed by gene*expression patterns.Pharmacoproteomics provides a more functionalrepresentation of patient*to*patient variationthan that &hich is provided by genotyping#and therfore also contributes to personalizedmedicine. A 5pharmacometabonomic6 approachinvolves the study of metabolites and ho& thesecan contribute to personalizing drug treatment.

Human genomeIn 7une $222# at a gala televised press conferenceattended by the then 8/ President 9ill lintonand 8; Prime ?I,# $2"2@ 7>0@# 30312 I//? "0"*210" 347

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long history of science &ith only a fe& basic sciencediscoveries being translated into medicine#&hat has been the progress in both genomicsand healthcare'Genomics revolution

The rst post*genome decade &as characterized

by spectacular advances in genome science.The dramatic improvement in 4?A sequencingtechnology &ith a drop of costs by approximately"0#222*fold has increased the base pairsof sequence in databases from J billion in $222to $2 billion bases today# in $2"2 !1%. T&odozen human genomes have been completelysequences and published# &hile approximatelyanother $22 have been sequenced but not published!0%.


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and points out that# because of the myriad phenotypictraits as clinical data# more po&erfulcomputational strategies &ill be needed to lin(phenotype to genotype !J%.Indeed# there are several reasons explainingthe limitations in translating genomic discoveries

into medical practice.


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disease*ris( prediction !$3#$0%.'ersonali(ed M 34% edicine >$2"2@ 7>0@ future science group

Editorial ;atsios Q Mou(os&he challenge' genotype(phenotypemap pre"iction9oth genotype and phenotype are crucial fordisease*ris( prediction among individuals !#J%.As the costs drop and quality of sequencing datais improved# the catalog of driver mutations forma+or diseases &ill be improved. ,igh*qualityclinical and therapeutic data >phenotype@ areavailable from large*scale randomized controlledtrials and databases. The bigger challenge no&is ho& to lin( all these phenotype data to thegenotyping data.

#human genomes and cancer genomesthat have +een completely se6uenced, and

the revolution in genomics have togetherrevealed the high complexity andheterogeneity of cancer and other common

complex diseases.$Oet the nonlinear relationship bet&een genotypeand phenotype represents the biggest challengein biomedical and mathematical sciences./everal computational strategies are being developedto predict genegene and geneenvironmentinteractions !$"%. 9ionet&or(s modeling representsone of the most promising research elds to&ardsa genotypephenotype*based personalizedmedicine !$1%. E-orts are under&ay to integrate

genotyping and molecular data into molecularnet&or( modeling to predict such outcomes !$2%./ystems biology# oncology and medicine open upne& &ays to understand complex biological systemsand ho& it could be possible to lin( genomicdata &ith clinical data and disease. This &ouldlead the &ay to understanding the pathogenesis ofdisease and biomar(ers for disease ris( predictionand preventions could be developed !"#$2#$$#$N$J%.

ConclusionAt the end of the rst post*genomic era &ith itsexplosion in sequencing technology# importantadvances and insights into genetic variation and

molecular mechanisms underlying human diversityhave improved our understanding of the complexityof life and disease heterogeneity. ,o&ever#the dramatic increase in the number of humangenomes and cancer genomes that have been completelysequenced# and the revolution in genomicshave together revealed the high complexity andheterogeneity of cancer and other common complexdiseases. This complexity of an unpreceded


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level explains the little impact# at least for nothat genomics has in a day*to*day clinical practice.

This suggests the need for an internationalnet&or( of scientic collaboration and conceptualinnovation to overcome a myriad of problems#and the labyrinth of life and disease complexity

to achieve personalized medicine!$30%

.)inancial competing interests "isclosure-he authors have no relevant a7liations or 8nancialinvolvement 9ith any organi(ation or entity 9ith a 8nancialinterest in or 8nancial con:ict 9ith the su+;ect matteror materials discussed in the manuscript. -his includesemployment, consultancies, honoraria, stoc o9nership oroptions, expert testimony, grants or patents received orpending, or royalties.$22"@.$ enter 7# Adams $2"[email protected] ,uman genome at ten: the sequenceexplosion. $J@# N2N">$2"2@. ollins =: ,as the revolution arrived' $J@# N0N1 >$2"[email protected] enter 7: $2"2@. /tratton $2"2@."$ /hah /P# $22@."0 9erou(him M# $2"2@."1 ,eppner ),: Tumor heterogeneity.


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)ancer >es. 00>N@# $$1$$N1 >"J0@."N ,e O# Bu 7# 4ressman 4# Iacobuzio*4onahue et al.: ,eteroplasmic mitochondrial4?A mutations in normal and tumour cells.$JJ@# N"2N"0 >$2"2@."7ones /# Rhang S# Parsons 4B: ore signalingpath&ays in human pancreatic cancers revealedby global genomic analyses. Science 3$">1J@#

"J2""J2N >$22J@."J ,anahan 4# Beinberg MA: The hallmar(s ofcancer. )ell "22# 12 >$222@.

future science group &&&.futuremedicine.com 34+

Individual genomes Q personalized medicine: life diversity Q complexity

Editorial" Mou(os 4,: /ystems medicine: a real approachfor future personalized oncology''harmacogenomics "">3@# $J3$J >$2"2@.$2 /chadt EE: $22J@.$0 Bacholder /# ,artge P# Prentice M et al.:Performance of common genetic variants inbreast*cancer ris( models. ""@# JN3 >$2"2@.$1 Mou(os 4,: 9ionet&or(s*basedpersonalized medicine versuscomparative-e-ectiveness research orharmonization of both in cancer

management' ?xpert >ev. Mol. Diagn."2>3@# $0$12 >$2"2@.$N Beinberg M: Point: hypotheses rst. $J@# NJ >$2"2@.$ Mou(os 4,# Riogas 4: =rom tumor size and,EM$ status to systems oncology for veryearly breast cancer treatment. ?xpert >ev.%nticancer -her. "2>$@# "$3"$J >$2"2@.$J Mou(os 4,: ?ovel clinico*genome net&or(modeling for revolutionizinggenotypephenotype*based personalizedcancer care. ?xpert >ev. Mol. Diagn. "2>"@#330J >$2"2@.$ Riogas 4# Mou(os 4,: )enetics and personalgenomics for personalized breast cancersurgery: progress and challenges in research

and clinical practice.%nn. Surg. =ncol. "N>@#"""J$ >[email protected] Mou(os 4,: Personalized cancer diagnosticsand therapeutics. ?xpert >ev. Mol. Diagn.>3@# $$$$ >[email protected]" Mou(os 4,: Madiation therapy for breastcancer. "3@# "3N$Lauthor reply "3N3 >[email protected]$ Mou(os 4,: Targeting gastric cancer &ithtrastuzumab: ne& clinical practice andinnovative developments to overcomeresistance.%nn. Surg. =ncol. "# "0"


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>$2"[email protected] Mou(os 4,: T&enty*Kne*)ene Assay:challenges and promises in translatingpersonal genomics and &hole*genome scansinto personalized treatment of breast cancer.@. )lin. =ncol. $>J@# "33"33J >[email protected] Mou(os 4,: Personal genomics andgenome*&ide association studies: novel

discoveries but limitations for practicalpersonalized medicine.%nn. Surg. =ncol."N>3@# $3 >$22@.

3,- future science group

Editorial ;atsios Q Mou(os'ersonali(ed Medicine >$2"2@ 7>0@

un studiu pt ggenetica la ubb cluj copiat din pdf

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