Next-generation, genome sequencing-based biomarkers: concerns and challenges for medical practice
2010; Future Medicine; Volume: 4; Issue: 4 Linguagem: Inglês
10.2217/bmm.10.70
ISSN1752-0371
Autores Tópico(s)Ferroptosis and cancer prognosis
ResumoBiomarkers in MedicineVol. 4, No. 4 General content - EditorialFree AccessNext-generation, genome sequencing-based biomarkers: concerns and challenges for medical practiceDimitrios H RoukosDimitrios H RoukosPersonalized Cancer Medicine, Biobank, Ioannina University School of Medicine, Ioannina, 45110 Greece and Department of Surgery, Ioannina University School of Medicine, Ioannina, 45110 Greece. Published Online:11 Aug 2010https://doi.org/10.2217/bmm.10.70AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Keywords: biomarkergenome sequencinggenome-wide association studiesIn their day-to-day clinical practice, physicians are facing the adverse effects and limited effectiveness of currently used drugs in the treatment of major diseases. Biomarkers represent the great promise for improving prevention and treatment of complex common diseases including cancer, cardiovascular disease and diabetes. However, the clinical implications of basic and translational research efforts are modest. Given the genetic variation among patients with the same disease (phenotype) and the current genomic revolution that is enabling us to identify genetic differences, how optimistic can we be for a new generation of robust biomarkers in medicine?The clinical need for prognostic and predictive markers has guided basic and translational sciences to offer clinicians new genetic and molecular tools that drive decision-making and allow tailoring of the best prevention or treatment in individual patients. The intensive research effort for developing biomarkers could be chronologically classified into four fields: the use of traditional clinicopathologic features and environmental factors, including lifestyle, classic single-gene molecular research, preliminary genome-wide association studies and complete genome sequencing and molecular networks, which are currently being used.Conventional clinical factorsIt is widely known that obesity, lack of physical activity, raised cholesterol, a low intake of fruit and vegetables, smoking, alcohol and several other factors increase the risk of common diseases such as cardiovascular diseases, diabetes and cancer. However, even using the combination of all these, along with conventional markers that use algorithmic approaches, is unable to accurately predict the disease risk in different individuals.Traditional single-gene molecular researchThe next research step focused on better understanding of molecular mechanisms underlying the pathogenesis of diseases. For example, prostate-specific antigen levels indicate a risk of prostate cancer and have been widely used for clinical screening. However, for complex multifactorial diseases, such as prostate cancer, the clinical use of such measurements has limitations for accurate individual risk predictions and general population screening [1]. In cancer treatment, the tumor node metastasis staging system and clinicopathologic features are the standard tools currently used for surgery, radiotherapy and systemic therapeutic decisions [2], but its modest ability to discriminate between responder and nonresponder patients is widely recognized.Several research strategies and scientific fields have been developed for personalized medicine. Pharmacogenetics, studying genetic associations with drug efficacy and toxicity, has led to the development of several enzymes with the most important belonging to the family of cytochrome P450 [3]. The primary aim is to predict the adverse effects for the guidance of individualized treatment. Although the term pharmacogenomics overlaps with pharmacogenetics, it is distinct owing to the fact that it evaluates the application of genomics to drug discovery. Pharmacogenomics evaluates the mechanism of action of drugs on cells as revealed by gene-expression patterns. Pharmacoproteomics provides a more functional representation of patient-to-patient variation than that provided by genotyping, which contributes to personalized medicine. A 'pharmacometabonomic' approach involves the study of metabolites and how these can contribute to personalizing drug treatment.Multigene assays & genome-wide association studiesThe advent of high-throughput technology over the past 10 years has revolutionized basic and translational research strategies. The massively parallel sequencing platforms allow the profiling of the expression of hundreds of genes at a time. Several gene-expression profiling studies using microarrays and real-time PCR techniques have resulted in the development of a molecular classification of breast cancer and multigene assays. It was believed that such a multigene approach could lead to more individualized therapeutic decisions in an era of personalized medicine.Of the multiple multigene assays proposed to have prognostic or predictive value for many solid tumors, including breast cancer, two gene signatures have most rapidly progressed: the 21-gene assay and the 70-gene signature. The 21-gene recurrence score was developed to identify high-risk patients of distant recurrence among those with node-negative, estrogen receptor-positive early breast cancer [4]. The efficacy of this genetic tool, which has now been commercialized (Oncotype DX), is tested in the large-scale Phase III trial (Trial Assigning Individual Option for Treatment [TAILORx]) in the USA. The 70-gene signature has been approved by the US FDA as a genetic test for women with node-negative early breast cancer. It was believed that it would be a robust predictor of distant metastatic risk, enabling adjuvant chemotherapy for high-risk patients [5]. This genetic tool has been commercialized (MammaPrint) and is now being tested in a Phase III randomized controlled trial in Europe (Microarray in Node-Negative Disease Avoids Chemotherapy [MINDACT] trial).However, gene-expression profiling studies alone have substantial limitations. There are two main arguments for the uncertainty of the clinical utility of these multigene classifiers. There is a series of methodological disadvantages in both the original training sets developed and the subsequent observational validation studies to assess the predictive power of these classifiers [6,7]. However, the clinical utility of Oncotype Dx and MammaPrint assays is not known and only the result of the ongoing Phase III trials will definitely indicate the robustness of these genetic tools.In the prevention setting, genome-wide association studies (GWAS) with potential identification of genetic variation for disease risk prediction over the last 3 years have been met with enthusiasm. Based on sequence databases, microchips with tens of thousands of genetic variants, including single-nucleotide polymorphisms and copy-number variants were developed. These chips have allowed GWAS to identify a wealth of novel genetic variants associated with diseases. As a result, biotechnology companies, including Celera (CA, USA) and deCODE Genetics (Reykjavik, Iceland), have had to rethink their optimistic assumption that selling human genetic information could turn a huge profit from personal genetic testing.Summarizing the results of a GWAS examining personalized risk prediction, two categories of genetic variants have emerged. The first group includes very rare mutations in the general population that raise the risk of diseases, such as schizophrenia, epilepsy and autism, by up to 20-fold. These discoveries have clinical applications in risk prediction, but owing to their rarity, the benefits are limited to only a few individuals. The second includes common genetic variants, but they confer only a very small increase in disease risk and, therefore, have little or no clinical utility [8,9]. Indeed, recently, nine and ten single-nucleotide polymorphisms identified by GWAS to be involved in cardiovascular disease and breast cancer, respectively, did not improve disease risk predictions in two large studies [10,11].Complete genome sequencing When the first draft of the complete human genome sequence was announced, The White House press statement articulated the hope, felt by many, that this landmark achievement would "lead to a new era of molecular medicine, an era that will bring new ways to prevent, diagnose, treat and cure disease". Today, 10 years on, where do we stand and where we will be 10 years from now?Sequencing technology explosion The first postgenome decade was characterized by spectacular advances in genome science. The dramatic improvement in DNA-sequencing technology along with a dramatic drop of sequencing costs has increased the numbers of base pairs sequenced in databases from 8 billion in 2000 to 270 billion today [12]. To date, there have been two dozen publications of complete-sequence human genomes and close to 200 unpublished ones [13]. Several other international projects and consortia, such as the Encyclopedia of DNA Elements (ENCODE), provide important information on coding and noncoding DNA, aiming to improve our understanding of every functional element in the human genome. Much noncoding DNA may have a regulatory role; small RNAs of different varieties appear to control gene expression at the level of both DNA and RNA transcription in ways that are still only beginning to become clear [14].As complete-genome sequencing data emerge, it becomes clear that the more we learn, the bigger the problem of understanding the life mysteries of biodiversity, aging and complex disease pathogenesis and evolution, such as cancer, becomes [15]. However, the impact of the genomic revolution on medicine and health is limited. To move forward to the future, Collins considers five important key lessons: personalized medicine, technology, policy, partnerships and pharmacogenomics [16]. Venter emphasizes the need for research in linking genotype to phenotype and points out that owing to the myriad of phenotypic traits, more powerful computational strategies will be needed to link phenotype to genotype [17].Predicting the genotype–phenotype relationshipIndeed, there are several reasons explaining the limitations in translating genomic discoveries into medical practice. Major hurdles that must be overcome in order to develop robust biomarkers for improving health in the future can be summarized into two directions. First, to complete the somatic mutation catalogue of the disorders. Second, to understand complex interactions between these genetic variants, between genes and environment or lifestyle, and between various human cells.ChallengesMany challenges exist despite advances with the latest technology. First, DNA changes include not only point mutations, such as nucleotide insertions, deletions and single-nucleotide polymorphisms, but also genomic rearrangements and copy-number changes. For example, complete genome sequencing for breast, lung and other major cancers have revealed a huge number of mutation and widespread variability [18–24]. Second, the discrimination between causal (driver) mutations and non-causal (passenger) mutations that are identified by genome sequencing studies is still difficult. Third, the bigger challenge is to understand how the complex gene–gene, protein–protein, gene–environment and intratumoral cell–cell interactions occur in a timely and very dynamic process, for example in cancer.Molecular networksNot only genotyping but also phenotype data are crucial for disease risk prediction and progression in individual persons [17,25]. As the costs drop and the quality of sequencing data are improved, the catalogue of driver mutations for major diseases will be improved. High-quality clinical and therapeutic data (phenotype) are available from large-scale randomized controlled trials and databases. The bigger challenge is how to link all these data with genotyping.However, the nonlinear relationship between genotype and phenotype represents the biggest challenge in biomedical and mathematical sciences. Several computational strategies are being developed to predict gene–gene and gene–environment interactions [26]. Bionetwork modeling represents one of the most promising research fields towards genotype–phenotype-based personalized medicine [27]. Efforts are underway to integrate genotyping and molecular data into the modeling of molecular networks to predict outcomes [27]. Systems biology, oncology and medicine open new ways to understand complex biological systems and explain how it could be possible to link genomic data with clinical data and diseases for understanding pathogenesis and developing biomarkers for disease risk prediction and prevention [9,26–37].ConclusionPhysicians urgently need biomarkers for improving the healthcare of their patients. However, despite effort with traditional single-gene molecular research and preliminary GWAS, clinical implications are modest and valid concerns exist for this research direction.Current efforts to complete the driver mutations catalogue for each common complex disease, and to understand biological and molecular networks provides an exciting field for novel biomarkers. However, the road to reaching medical applications is still long and many challenges must be overcome.Financial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.Bibliography1 Lin K, Lipsitz R, Miller T, Janakiraman S; US Preventive Services Task Force: Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann. Intern. Med.149(3),192–199 (2008).Crossref, Medline, Google Scholar2 Edge SE, Byrd DR, Carducci MA, Compton CA (Eds): AJCC Cancer Staging Manual (7th Edition). Springer, NY, USA (2009).Google Scholar3 Roederer MW: Cytochrome P450 enzymes and genotype-guided drug therapy. Curr. Opin. Mol. Ther.11(6),632–640 (2009).Medline, CAS, Google Scholar4 Paik S, Shak S, Tang G et al.: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N. Engl. J. Med.351,2817–2826 (2004).Crossref, Medline, CAS, Google Scholar5 van de Vijver MJ, He YD, van't Veer LJ et al.: A gene-expression signature as a predictor of survival in breast cancer. N. Engl. J. Med.347,1999–2009 (2002).Crossref, Medline, CAS, Google Scholar6 O'Shaughnessy JA: Molecular signatures predict outcomes of breast cancer. N. Engl. J. Med.355(6),615–617 (2006).Crossref, Medline, Google Scholar7 Huang CC, Bredel M: Use of gene signatures to improve risk estimation in cancer. JAMA299(13),1605–1606 (2008).Crossref, Medline, CAS, Google Scholar8 Goldstein DB: 2020 visions. Personalized medicine. Nature463(7277),26–32 (2010).Crossref, Medline, Google Scholar9 Roukos DH: Genome-wide association studies: how predictable is a person's cancer risk? Expert Rev. Anticancer Ther.9(4),389–392 (2009).Crossref, Medline, Google Scholar10 Kathiresan S, Melander O, Anevski D et al.: Polymorphisms associated with cholesterol and risk of cardiovascular events. N. Engl. J. Med.358(12),1240–1249 (2008).Crossref, Medline, CAS, Google Scholar11 Wacholder S, Hartge P, Prentice R et al.: Performance of common genetic variants in breast-cancer risk models. N. Engl. J. Med.362(11),986–993 (2010).Crossref, Medline, CAS, Google Scholar12 No authors listed. Human genome at ten: the sequence explosion. Nature464(7289),670–671 (2010).Crossref, Medline, Google Scholar13 No authors listed. The human genome at ten. Nature464(7289),649–650 (2010).Crossref, Medline, Google Scholar14 Check Hayden E: Human genome at ten: life is complicated. Nature464(7289),664–667 (2010).Crossref, Medline, Google Scholar15 Ledford H: Big science: the cancer genome challenge. Nature464(7291),972–974 (2010).Crossref, Medline, CAS, Google Scholar16 Collins F: Has the revolution arrived? Nature464(7289),674–675 (2010).Crossref, Medline, CAS, Google Scholar17 Venter JC: Multiple personal genomes await. Nature464(7289),676–677 (2010).Crossref, Medline, CAS, Google Scholar18 Stratton MR, Campbell PJ, Futreal PA: The cancer genome. Nature458(7239),719–724 (2009).Crossref, Medline, CAS, Google Scholar19 Pleasance ED, Stephens PJ, O'Meara S et al.: A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature463(7278),184–190 (2010).Crossref, Medline, CAS, Google Scholar20 Pleasance ED, Cheetham RK, Stephens PJ et al.: A comprehensive catalogue of somatic mutations from a human cancer genome. Nature463(7278),191–196.Crossref, Medline, Google Scholar21 Stephens PJ, McBride DJ, Lin ML et al.: Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature462(7276),1005–1010 (2009).Crossref, Google Scholar22 Beroukhim R, Mermel CH, Porter D et al.: The landscape of somatic copy-number alteration across human cancers. Nature463(7283),899–905 (2010).Crossref, Medline, CAS, Google Scholar23 Ding L, Ellis MJ, Li S et al.: Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature464(7 291),999–1005 (2010).Crossref, Medline, CAS, Google Scholar24 Jones S, Zhang X, Parsons DW: Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science321(5897),1801–1806 (2008).Crossref, Medline, CAS, Google Scholar25 Roukos DH: Novel clinico-genome network modeling for revolutionizing genotype–phenotype-based personalized cancer care. Expert Rev. Mol. Diagn.10(1),33–48 (2010).Crossref, Medline, CAS, Google Scholar26 Rockman MV: Reverse engineering the genotype–phenotype map with natural genetic variation. Nature456,738–744 (2008).Crossref, Medline, CAS, Google Scholar27 Roukos DH: Bionetworks-based personalized medicine versus comparative-effectiveness research or harmonization of both in cancer management? Expert Rev. Mol. Diagn.10(3),247–250 (2010).Crossref, Medline, Google Scholar28 Roukos DH: Systems medicine: a real approach for future personalized oncology? Pharmacogenomics11(3),283–287 (2010).Link, Google Scholar29 Schadt EE: Molecular networks as sensors and drivers of common human diseases. Nature461(7261),218–223 (2009).Crossref, Medline, CAS, Google Scholar30 Weinberg R: Point: hypotheses first. Nature464(7289),678 (2010).Crossref, Medline, Google Scholar31 Roukos DH, Ziogas D: From tumor size and HER2 status to systems oncology for very early breast cancer treatment. Expert Rev. Anticancer Ther.10(2),123–128 (2010).Crossref, Medline, CAS, Google Scholar32 Roukos DH: Breast cancer outcomes: the crucial role of the breast surgeon in the era of personal genetics and systems biology. Ann. Surg.249(6),1067–1068 (2009).Crossref, Medline, Google Scholar33 Ziogas D, Roukos DH: Genetics and personal genomics for personalized breast cancer surgery: progress and challenges in research and clinical practice. Ann. Surg. Oncol.16(7),1771–1782 (2009).Crossref, Medline, Google Scholar34 Roukos DH: Personalized cancer diagnostics and therapeutics. Expert Rev. Mol. Diagn.9(3),227–229 (2009).Crossref, Medline, Google Scholar35 Roukos DH: Beyond HER2 and trastuzumab: heterogeneity, systems biology, and cancer origin research may guide the future for personalized treatment of very early but aggressive breast cancer. J. Clin. Oncol.28(17),E279–E280 (2010).Crossref, Medline, Google Scholar36 Roukos DH: Targeting gastric cancer with trastuzumab: new clinical practice and innovative developments to overcome resistance.Ann. Surg. Oncol.17,14–17 (2010).Crossref, Medline, Google Scholar37 Roukos DH: Personal genomics and genome-wide association studies: novel discoveries but limitations for practical personalized medicine. Ann. Surg. Oncol.16(3),772–773 (2009).Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited ByPrecision Medicine of Autoimmune Diseases25 August 2021Deciphering Potential Correlations between New Biomarkers and Pattern Classification in Chinese Medicine by Bioinformatics: Two Examples of Rheumatoid Arthritis19 October 2018 | Chinese Journal of Integrative Medicine, Vol. 27, No. 6Clinical Genome Data Model (cGDM) provides Interactive Clinical Decision Support for Precision Medicine29 January 2020 | Scientific Reports, Vol. 10, No. 1Cascaded Wx: A Novel Prognosis-Related Feature Selection Framework in Human Lung Adenocarcinoma Transcriptomes19 July 2019 | Frontiers in Genetics, Vol. 10Identification of key genes fluctuated induced by avian leukemia virus (ALV-J) infection in chicken cells1 December 2017 | In Vitro Cellular & Developmental Biology - Animal, Vol. 54, No. 1Label‐Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes6 March 2017 | Advanced Science, Vol. 4, No. 5Past, current and future approaches to querying MAPK pathway activation: status and clinical implicationsKen CN Chang & Matthew J Marton1 December 2014 | Personalized Medicine, Vol. 11, No. 8Recent Advances in the Molecular Characterization of Circulating Tumor Cells13 March 2014 | Cancers, Vol. 6, No. 1The fall and rise of pharmacology – (Re-)defining the discipline?Biochemical Pharmacology, Vol. 87, No. 1From single protein to colorectal cancer genome landscape and network biology-based biomarkers27 February 2013 | Surgical Endoscopy, Vol. 27, No. 8Colorectal cancer liver metastases: advances in minimally invasive surgery and genome sequencing-based discoveries13 December 2012 | Surgical Endoscopy, Vol. 27, No. 5Next-generation, genome- and mutational landscape heterogeneity-based novel biomarkers for personalized neoadjuvant treatment and laparoscopic rectal cancer resection6 October 2012 | Surgical Endoscopy, Vol. 27, No. 4GIST: advances in tyrosine kinase inhibitors enhance laparoscopic resection even in advanced disease24 October 2012 | Surgical Endoscopy, Vol. 27, No. 4Network-based drugs: promise and clinical challenges in cardiovascular disease9 January 2014 | Expert Review of Proteomics, Vol. 10, No. 2Gene expression 'signature' limitations and genome architecture-based perspectives for robust cancer biomarkersChristos S Katsios, Costas Papaloukas, Dimitrios H Roukos & George Baltogiannis6 February 2013 | Biomarkers in Medicine, Vol. 7, No. 1Integrating NGS and third-generation sequencing technologies into clinical genomic medicineMargaret Tzaphlidou, Costas Papaloukas & Dimitrios H Roukos13 February 2013Dynamic imaging in medicine and network biology18 July 2012 | Surgical Endoscopy, Vol. 27, No. 2From targeted monotherapy to combined BRAF–MEK inhibitors and integrated genome analysis for melanoma treatmentDimitrios H Roukos, Costas Papaloukas & Margaret Tzaphlidou19 December 2012 | Future Oncology, Vol. 9, No. 1Deep sequencing and integrative genome analysis: approaching a new class of biomarkers and therapeutic targets for breast cancerGeorge Zografos, Theodore Liakakos & Dimitrios H Roukos19 December 2012 | Pharmacogenomics, Vol. 14, No. 1Predictive medicine and esophageal cancer response to preoperative chemotherapy22 June 2012 | Surgical Endoscopy, Vol. 27, No. 1Targeted therapy for colorectal cancer resistance to EGF receptor antibodies and new trends10 January 2014 | Expert Review of Gastroenterology & Hepatology, Vol. 7, No. 1Trastuzumab emtansine for advanced HER2-positive breast cancer and beyond: genome landscape-based targets10 January 2014 | Expert Review of Anticancer Therapy, Vol. 13, No. 1From next-generation sequencing to nanopore sequencing technology: paving the way to personalized genomic medicine9 January 2014 | Expert Review of Medical Devices, Vol. 10, No. 1Integrated clinical genomics: new horizon for diagnostic and biomarker discoveries in cancer9 January 2014 | Expert Review of Molecular Diagnostics, Vol. 13, No. 1The long-term efficacy of laparoscopic surgery in early and advanced gastric cancer27 April 2012 | Surgical Endoscopy, Vol. 26, No. 12Expanding laparoscopic gastrectomy for gastric cancer outside Korea and Japan26 June 2012 | Surgical Endoscopy, Vol. 26, No. 12Biomarkers and Their Potential Use in TransplantationProceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences, Vol. 66, No. 6Novel Wnt signaling and other pathway inhibitors in the colorectal cancer genomic landscape eraDimitrios H Roukos, Demosthenes E Ziogas, Costas Papaloukas & George Baltogiannis14 November 2012 | Future Oncology, Vol. 8, No. 11Personalized medicine for laparoscopic gastrectomy in gastric cancer2 May 2012 | Surgical Endoscopy, Vol. 26, No. 11Genome-based diagnostics and predictive tools: a new epoch for breast cancer managementDemosthenes E Ziogas, George Baltogiannis, John Spiliotis, Margaret Tzaphlidou & Dimitrios H Roukos6 November 2012 | Future Oncology, Vol. 8, No. 10De novo mutations, protein–protein interactions and functional regulatory networks toward novel diagnostics in autism9 January 2014 | Expert Review of Proteomics, Vol. 9, No. 5Assessing tumor heterogeneity and emergence mutations using next-generation sequencing for overcoming cancer drugs resistance10 January 2014 | Expert Review of Anticancer Therapy, Vol. 12, No. 10Next-generation sequencing-based testing for cancer mutational landscape diversity: clinical implications?9 January 2014 | Expert Review of Molecular Diagnostics, Vol. 12, No. 7Histology classification challenges for the endoscopic treatment of early gastric cancer6 January 2012 | Surgical Endoscopy, Vol. 26, No. 7Targeted therapy: overcoming drug resistance with clinical cancer genome10 January 2014 | Expert Review of Anticancer Therapy, Vol. 12, No. 7Emerging personalized oncology: sequencing and systems strategiesWilliam Cho, Demosthenes E Ziogas, Christos Katsios & Dimitrios H Roukos5 July 2012 | Future Oncology, Vol. 8, No. 6Translating Cancer Genomes Sequencing Revolution into Surgical Oncology PracticeJournal of Surgical Research, Vol. 173, No. 2Timing of laparoscopic surgery in the neoadjuvant treatment of rectal cancer23 September 2011 | Surgical Endoscopy, Vol. 26, No. 3Laparoscopic gastrectomy and impact on recurrence of gastric cancer20 October 2011 | Surgical Endoscopy, Vol. 26, No. 3Robotic surgery and limitations10 September 2011 | Surgical Endoscopy, Vol. 26, No. 2Endoscopic and laparoscopic ultrasonography used to predict tumor staging and improve therapeutic decisions for upper gastrointestinal tract cancer26 July 2011 | Surgical Endoscopy, Vol. 26, No. 1Single-Variant and Multi-Variant Trend Tests for Genetic Association with Next-Generation Sequencing That Are Robust to Sequencing Error11 April 2013 | Human Heredity, Vol. 74, No. 3-4Robotic versus laparoscopic surgery for rectal cancer and cost-effectiveness analysis22 June 2011 | Surgical Endoscopy, Vol. 25, No. 12Erlotinib and Pancreatic Adenocarcinoma: Uncertainty and Hope1 June 2011 | Annals of Surgical Oncology, Vol. 18, No. S3Slow Progress in Predicting and Preventing Fatal Gastric Cancer Peritoneal Recurrence21 June 2011 | Annals of Surgical Oncology, Vol. 18, No. S3High Ligation of Inferior Mesenteric Artery: A Standard Procedure for Colorectal Cancer?2 July 2011 | Annals of Surgical Oncology, Vol. 18, No. S3Moving Away From Axillary Lymph Node Dissection Indicates Practice-Changing Trials6 July 2011 | Annals of Surgical Oncology, Vol. 18, No. S3BRCA Testing Changes Decision on Breast Cancer Surgery but Evidence for Benefit Is Still Scarce15 July 2011 | Annals of Surgical Oncology, Vol. 18, No. S3Preventive and Therapeutic Implications of Positive CDH1 Testing in Diffuse Gastric Cancer15 July 2011 | Annals of Surgical Oncology, Vol. 18, No. S3Strategy for Nonresponder Breast Cancer Patients to Neoadjuvant Treatment16 August 2011 | Annals of Surgical Oncology, Vol. 18, No. S3HER2-Positive Gastric Cancer16 August 2011 | Annals of Surgical Oncology, Vol. 18, No. S3Sentinel node biopsy in laparoscopic surgical oncology19 May 2011 | Surgical Endoscopy, Vol. 25, No. 11Thoracolaparoscopic esophagectomy: further improvement in the multimodal treatment of esophageal cancer13 April 2011 | Surgical Endoscopy, Vol. 25, No. 10Totally laparoscopic total gastrectomy and the challenge of esophagojejunostomy13 April 2011 | Surgical Endoscopy, Vol. 25, No. 10Pancreatic Cancer: The Challenge of the Future in Tumorigenesis-based Prevention16 March 2011 | World Journal of Surgery, Vol. 35, No. 9Genotyping Gastric Cancer4 March 2011 | World Journal of Surgery, Vol. 35, No. 8Mediastinal lymphadenopathy: assessing clinical utility of EUS-FNA8 February 2011 | Surgical Endoscopy, Vol. 25, No. 8Proximal gastric cancer: advances of laparoscopic surgery17 March 2011 | Surgical Endoscopy, Vol. 25, No. 8Single-incision laparoscopic surgery for colorectal cancer17 March 2011 | Surgical Endoscopy, Vol. 25, No. 8Linking epidermal growth factor plasma levels with the prognosis and treatment response of colorectal cancer patients treated with a minimally invasive approach: does it have clinical utility?17 March 2011 | Surgical Endoscopy, Vol. 25, No. 8Challenges with identification of angiogenesis biomarkers in cancer13 April 2011 | Surgical Endoscopy, Vol. 25, No. 8Laparoscopic and robotic-assisted D2 surgery for gastric cancer: a reality in Europe?7 February 2011 | Surgical Endoscopy, Vol. 25, No. 7Optimizing Preoperative Management of Rectal Cancer30 December 2010 | World Journal of Surgery, Vol. 35, No. 6Assessing superiority: intracorporeal versus extracorporeal anastomosis for laparoscopic colon resection26 October 2010 | Surgical Endoscopy, Vol. 25, No. 6Laparoscopic restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis and impact of anti-tumor necrosis factor on postoperative outcomes26 October 2010 | Surgical Endoscopy, Vol. 25, No. 6Nonepithelial, submucosal gastric tumors: is laparoscopic wedge resection the optimal treatment?18 November 2010 | Surgical Endoscopy, Vol. 25, No. 6Histological and Immediate Postoperative Outcome after Preoperative Cetuximab: Case-matched Control Study24 December 2010 | World Journal of Surgery, Vol. 35, No. 5Right colectomy: is it a safe and feasible totally laparoscopic approach with transvaginal specimen extraction23 October 2010 | Surgical Endoscopy, Vol. 25, No. 5Recovery after laparoscopic right hemicolectomy for colon cancer26 October 2010 | Surgical Endoscopy, Vol. 25, No. 5Exploring indications for laparoscopic primary tumor resection in metastatic colorectal cancer6 November 2010 | Surgical Endoscopy, Vol. 25, No. 5Two-Stage Breast Cancer Screening in the Developing World21 September 2010 | World Journal of Surgery, Vol. 35, No. 3Clinicopathologic Characteristics of Colorectal Cancer Patients with Synchronous and Metachronous Gastric Cancer19 November 2010 | World Journal of Surgery, Vol. 35, No. 3Innovative biomarker development for personalized medicine in breast cancer careGeorge C Zografos & Dimitrios H Roukos14 February 2011 | Biomarkers in Medicine, Vol. 5, No. 1Managing BRCA Mutation Carriers in China5 October 2010 | World Journal of Surgery, Vol. 35, No. 2Remnant Gastric Cancer: Can the Risk Be Predicted When Planning Initial Surgery?25 September 2010 | World Journal of Surgery, Vol. 35, No. 2Metachronous Cancer in the Stomach Remnant21 September 2010 | World Journal of Surgery, Vol. 35, No. 2Adjuvant S-1 Chemotherapy for Gastric Cancer and Peritoneal Wash21 September 2010 | World Journal of Surgery, Vol. 35, No. 2Innovation versus evidence: to trust direct-to-consumer personal genomic tests?9 January 2014 | Expert Review of Molecular Diagnostics, Vol. 11, No. 1Blood-based peptide, genetic, and epigenetic biomarkers for diagnosing gastrointestinal cancers10 November 2010 | Expert Opinion on Medical Diagnostics, Vol. 4, No. 6Next-generation sequencing and epigenome technologies: potential medical applications9 January 2014 | Expert Review of Medical Devices, Vol. 7, No. 6Colorectal cancer: cetuximab, KRAS , BRAF , PIK3CA mutations and beyond10 January 2014 | Expert Review of Gastroenterology & Hepatology, Vol. 4, No. 5Multigene assays and isolated tumor cells for early breast cancer treatment: time for bionetworks10 January 2014 | Expert Review of Anticancer Therapy, Vol. 10, No. 8 Vol. 4, No. 4 STAY CONNECTED Metrics History Published online 11 August 2010 Published in print August 2010 Information© Future Medicine LtdKeywordsbiomarkergenome sequencinggenome-wide association studiesFinancial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download
Referência(s)