Day 1 :
Keynote Forum
Jianhua Luo
University of Pittsburgh, USA
Keynote: Genome biomarkers of prostate cancer
Time : 09:55-10:30
Biography:
Jianhua Luo has been studying Molecular Pathology related to human malignancies since the last 24 years. Currently, he is a Professor of Pathology and Director of High Throughput Genome Center at University of Pittsburgh. In the last 16 years, he has been largely focusing on genetic and molecular mechanism of human prostate and hepatocellular carcinomas. In this period, his group has identified and characterized several genes that are related to prostate cancer and hepatocellular carcinoma, including SAPC, myopodin, CSR1, GPx3, ITGA7, MCM7, MT1h and GPC3. He has characterized several signaling pathways that play critical role in prostate cancer development, including Myopodin-ILK-MCM7 inhibitory signaling, myopodin-zyxin motility inhibition pathway, CSR1-CPSF3, CSR1-SF3A3 and CSR1-XIAP apoptotic pathways, MT1h-EHMT1 egigenomic signaling, ITGA7-HtrA2 tumor suppression pathway, GPx3-PIG3 cell death pathway, AR-MCM7 and MCM7-SF3B3 oncogenic pathways. He proposed prostate cancer field effect in 2002. He is one of the pioneers in utilizing high throughput gene expression and genome analyses to analyze field effects in prostate cancer and liver cancer. He is also the first in using methylation array and whole genome methylation sequencing to analyze prostate cancer. Recently, his group found that patterns of copy number variants of certain specific genome loci are predictive of prostate cancer clinical outcomes, regardless of tissue origin. His discovery of several novel fusion transcripts and their association with aggressive prostate cancer has brought significant new insight into the field of prostate cancer research. Overall, these findings advance our understanding on how cancer develops and behave, and lay down the foundation for better future diagnosis and treatment of human malignancies.
Abstract:
Accurate prediction of prostate cancer clinical courses remains elusive. In recent studies, we performed whole genome analysis on prostate cancers by combining Affymetrix SNP6.0 chip, whole genome sequencing and transcriptome sequencing. Our results showed that combination of genome copy number variance and novel fusion transcripts specific for cancer achieved high accuracy in predicting prostate cancer outcomes. The prediction model was further improved when these molecular criteria were combined with Nomogram or Gleason’s grading. Interestingly, some of these fusion genes are also present in a variety of human malignancies. One of these fusion genes, MAN2A1-FER appears a cancer driver since it induced cancer both in vivo and in vitro. Treatment of cancers with drugs specific for MAN2A1-FER signaling pathway produced dramatic improvement of metastasis and survival rate of animals xenografted with cancers positive for this fusion gene. Our analyses suggest that targeting therapy for fusion genes holds promise as an effective treatment for human cancers.
Keynote Forum
Martin Burow
DMB-Diagnostics GmbH, Germany
Keynote: Maintrac - A new clinical method for quantitative CTC diagnostic, treatment selection, monitoring and surveillance of patients
Time : 10:30-11:05
Biography:
Martin Burow completed his chemistry and biochemistry PhD at the University of Münster in 1993 and worked 3 years as a postdoctoral fellow for the Ministry of International Trade and Industry at the National Institute of Materials and Chemical Research (NIMC) in Tsukuba, Japan. After his return to Germany Dr. Burow started his career in the medical device industry and developed the Asian-Pacific markets for Brahms-Thermofisher in the field of medical diagnostics (thyroid, sepsis, prenatal and oncology). Later he started his own company (DMB-Diagnostics GmbH) to introduce highly innovative diagnostics worldwide for better treatment standards of oncological patients.
Abstract:
Maintrac® is a laboratory based method to quantify in a reproducible manner living circulating tumor cells. This way it is possible to do further analytic with these cells. Be it molecular genetic testing of certain tumor characteristics or surface protein determination for real pharmaceutical target identification.
Since these CTCs are alive it is possible to check all different chemotherapeutics and their killing rate on these CTCs. Best working medications can be selected before starting aggressive chemotherapies. Furthermore it is possible to monitor treatment success “just” by quantifying CTC over the cause of the therapy. Even during and after endocrine therapy it is possible to show how long to give i.e. Tamoxifen or when to switch to other, more efficient medication in case the cell number is increasing.
This method was developed over the last decade and works on all tumors deriving from epithelial origin (almost all solid tumors). We showed in several clinical trials with > 650 patients and > 100,000 measurement significant improvement for patients and the overall relapse free survival while being monitored and treated based on this method.
Maintrac is nowadays already used in clinical routine in ~30 countries worldwide
- Biomarkers: From discovery to application | Biomarkers: Validation and Verification | Predictive Cancer Biomarkers
Location: Sylt 5
Chair
Andreas Scherer
European Research Infrastructure for Translational Medicine, Netherlands
Co-Chair
Martin Kleinschmidt
Fraunhofer Institute for Cell Therapy and Immunology, Germany
Session Introduction
Bobbie Jo M Webb Robertson
Pacific Northwest National Laboratory, USA
Title: P-Mart: Interactive statistical resource to enable biomaker discovery from shotgun cancer proteomic datasets
Biography:
Bobbie Jo M Webb Robertson has a MS in Statistics and Operations Research and PhD in Decision Sciences and Engineering Systems from Rensselaer Polytechnic Institute. She leads a research portfolio in statistical and software development for high-throughput proteomic analyses with over 75 peer-reviewed publications in the field. In addition, she is currently the Technical Group Manager of the Applied Statistics and Computational Modeling Group at Pacific Northwest National Laboratory.
Abstract:
For the field of clinical proteomics to successfully identify new prognostics or diagnostics of disease or response to therapies requires not only requires high quality data with respect to the instrument, but also high quality statistical analysis of the data. However, one of the major challenges to the discovery of robust cancer biomarker candidates from global shotgun mass spectrometry (MS)-based proteomic experiments is processing these large and complex datasets in a manner that accounts for the underlying statistical hypothesis of interest. P-Mart is a new interactive web-based software environment that enables biomedical and biological scientists to perform in-depth analyses of global proteomics data without requiring knowledge of processing raw mass spectra or complex matrices of peptide abundances. P- Mart offers a series of statistical modules associated with quality assessment, peptide and protein statistics, protein quantification and exploratory data analyses. Currently, P-Mart offers access to multiple cancer proteomic datasets generated through the clinical proteomics tumor analysis consortium (CPTAC) at the peptide, gene and protein levels. Analyses are performed in P-Mart via customized workflows and interactive visualizations. P-Mart is funded through the National Cancer Institute’s Informatics Technology for Cancer Research (ITCR) program under grant U01-CA184738-01.
Andreas Scherer
University of Helsinki, Finland
Title: Irreproducibility in biomarker research and clinical development: A global challenge
Biography:
Andreas Scherer has been working in biomarker R&D in various roles in academia and industry for the past 17 years. Currently, he is Finland’s National Coordinator for EATRIS, the European Research Infrastructrue for Translational Medicine, and serves as Co-Chair of the EATRIS Biomarker Platform. He also has a role as Biomarker and Molecular Diagnostics Project Coordinator at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki. Since 2007, he has been Consultant for omics-based biomarker development in his own company, Spheromics.
Abstract:
Valid biomarkers are in high demand for drug development, playing an increasingly important role in clinical applications to support and enable e.g. patient stratification, drug selectivity and prediction of toxicity. Individual investigators are not always aware of the complexity of the steps from translating fundamental research findings to clinical applicability, thus facing an immense failure rate due to mostly irreproducible data, e.g. in the area of biomarker research. Efforts by individual groups to publish confirmatory datasets exist but are rare, maybe exemplified by some of our own research on biomarkers in clear cell renal cell carcinoma. However, clinical relevance of such data can only be tested by using large sample numbers and efforts by large teams of investigators. The European Research Infrastructure for Translational Medicine EATRIS is a distributed consortium with currently 80 academic centers in 11 European countries which supports translational medical research towards clinical applications. According to EATRIS’ vision to increase awareness of the challenges of translation from fundamental research to clinical application among investigators, we believe that international and global research scale can provide validatable insights into clinical biomarkers and other technologies, impacting clinical care worldwide. EATRIS currently establishes collaborations of global scale to develop strategic plans to reveal sources of irreproducibility in the pre-clinical space including the biomarker field, thus reducing the high attrition rate of drug development pipelines and identifying opportunities for data quality improvement, ultimately for the benefit of human healthcare.
Martin Kleinschmidt
Fraunhofer Institute for Cell Therapy and Immunology, Germany
Title: Combination of blood-based biomarkers and neuropsychological assessment enables reliable classification of tested subjects by controls, mild cognitive impairment and Alzheimer's disease
Biography:
Martin Kleinschmidt has received his PhD in 2004 from the Martin-Luther-University Halle-Wittenberg. At the Probiodrug AG, he was responsible for biophysical characterization of interactions by SPR, ITC and X-ray structure analysis. Later he was the Project Manager for assay development. In 2013 he changed over to Fraunhofer IZI-MWT and is now Head of lab clinical and biophysical analytics. He has published 17 papers in well-known journals and is currently Associated Editor for the Journal of Alzheimer’s Disease.
Abstract:
Current treatment of Alzheimer’s disease (AD) is initiated at stages where the brain has irrevocably lost numerous neurons. Simple biochemical tests to differentiate normal aging from prodromal or demented stages are needed. Current standards identifying preclinical AD are neuroimaging and cerebrospinal fluid (CSF) analysis, but these methods are more cost-effective and more invasive than blood-based biomarker assays. However; in contrast to the approved methods quantifying the AD biomarker amyloid β (Aβ), Tau and P-Tau in CSF, detection of these biomarkers in blood is much more difficult due to at least 10-fold lower concentrations, but the 100-fold higher overall protein content leading to massive interference in currently used assay systems. Therefore, an assay was developed isolating Aβ by a multivalent capture system which exploits avidity effects by interactions of several anti-Aβ antibodies to multiple epitopes of the Aβ molecule. In our study, all participants were classified by a comprehensive neuropsychological assessment into controls, mild cognitive impairment (MCI), and AD. Blood samples were analyzed for several Aβ species, pro-inflammatory markers, anti-Aβ autoantibodies, and ApoE allele status, respectively. Plasma Aβ(1-42) was significantly decreased in MCI and AD compared to controls and strongly correlates with carrying ApoE ε4 allele. Furthermore, the Aβ(1-42)/Aβ(1-40) ratio is stepwise decreased in controls, MCI and AD, differentiating these groups significantly. Autoantibodies against pyroglutamate-modified Aβ (pGlu-Aβ), but not unmodified Aβ, were significantly decreased in AD compared to MCI and controls. Interestingly, the autoantibodies don’t correlate with ApoE ε4, supporting the associated plasma Aβ analysis with additional and independent information.
Josephine Worseck
Metabolomic Discoveries GmbH, Germany
Title: Kenkodo – Mining of metabolomic profiles
Biography:
Josephine Worseck is the Head of Business Development at Metabolomic Discoveries and has a scientific background in the field of systems biology. Her research at the Max Planck Institute for Molecular Genetics has been focused on the integrative analysis of data derived from high-throughput ‘omics technologies. After six years of applied science, she is now responsible for the consulting of scientists that want to resolve complex biological questions by metabolomics.
Abstract:
The Kenkodo Kit -offered by the German biotech company Metabolomic Discoveries- reveals exciting insights into the relationship between lifestyle and biochemical blood composition. Kenkodo is the first personalized metabolism analysis that combines personal lifestyle data with cutting-edge blood analytics. Users benefit from an easy and convenient blood sampling at home and insights that help to optimize well-being and to avoid diseases. The Kenkodo companion app integrates, tracks and visualizes the impact of human lifestyle in relationship to their metabolism with the aim to improve personal health outcomes. Metabolomic Discoveries GmbH is a leading company in the field of diagnostic biomarker research. Using high-throughput GC/MS and LC/MS combined with bioinformatic methods, Metabolomic Discoveries identifies and quantifies endogenous metabolites in body fluid or tissue samples and develops them into powerful biomarkers.
Joon Kim
Korea University, Korea
Title: Ribosomal protein S3 secreted from various cancer cell lines is a possible cancer biomarker
Biography:
Joon Kim has completed his BS and MS from Seoul National University, PhD in Biochemistry from the University of California at Berkeley and Postdoctoral study from Harvard Medical School. He is a Professor in the Division of Life Sciences, and the Director of Radiation Safety and Management Center, Korea University, Seoul, Korea. He has published more than 150 papers in reputed journals
Abstract:
Ribosomal protein S3 (rpS3) has been known as a genuine component of the 40S ribosomal small subunit. However, it has been recently discovered that it has multiple other extra-ribosomal functions in apoptosis, cell cycle control, DNA repair etc. It has a DNA repair endonuclease activity which is related with various cancers. Recently, we have discovered that this protein is secreted as a dimer after glycosylation in the ER. It is secreted only from various cancer cell lines but not in normal cells. We also confirmed that rpS3 is secreted more into media from the more invasive cancer cell lines. The secretion pathway turned out to be an ER-Golgi dependent pathway. We propose that secreted rpS3 could be used as a useful marker for cancer or cell invasiveness.
Weimin Miao
Chinese Academy of Medical Sciences and Peking Union Medical College, China
Title: Fluorescence in situ hybridization (FISH): An increasingly demanded tool for biomarker research and personalized medicine
Biography:
Weimin Miao has obtained the Medical degree from Shanghai Second Military Medical Univeristy and has completed his PhD from Fudan University in China. He did his Post-doctoral studies from Harvard Medical School in US and McGill Univeristy in Canada. He used to work as an Assistant Professor in Univeristy of Tennessee. Currently he is Professor of Chinese Academy of Medical Sciences and Peking Union Medical College, a top medical research organization. He has published more than 50 papers in reputed journals. He also served as a Chief Scientist in VCANBIO company, developing advanced molecular diagnostic products for clinical use.
Abstract:
Extensive studies conducted over the last two decades have identified recurrent genomic abnormalities as potential driving factors underlying a variety of cancers. With respect to biomarker detection, a series of innovative high-throughput molecular tests, such as array-based comparative genome hybridization (aCGH), single nucleotide polymorphism (SNP) arrays and next generation sequencing, have recently been developed and incorporated into routine clinical practice. However, although it is a classical low-throughput cytogenetic test, fluorescence in situ hybridization (FISH) does not show signs of fading; on the contrary, it plays an increasingly important role in detecting specific biomarkers in solid and hematologic neoplasms and has therefore become an indispensable part of the rapidly developing field of personalized medicine. For example, FISH has become gold standards for detecting cancer biomarkers, such as BCR-ABL1, PML-Rara, Her-2, EML4-ALK, BRAF, ROS1 and FGFR. Many of these FISH assays are actually the companion diagnostic tests directly involved in the targeted therapies and personalized medicine. Furthermore, FISH, especially quntitative multi-gene FISH has been increasingly used for molecular pathology subtyping, disease stratification, therapeutic guidance and prognosis evaluation. In this talk, I will summariz recent advances in FISH application for both de novo discovery and routine diagnosis for chromosomal rearrangements and amplification or deletion of genomic components that are associated with the pathogenesis of various hematopoietic and non-hematopoietic malignancies. I will also briefly review the recent developments in FISH methodology. Finally, I will introduce a new methodology-sequential FISH that we have developed recently for multi-gene analysis at the single-cell level.
Shashwati Basak
Syngene International Ltd, Bangalore, India
Title: Quantitative PCR-based cancer biomarker assays in clinical trials
Biography:
Shashwati Basak serves as the Head and Sr. Lead Investigator of Clinical Genomics Group in Exploratory Clinical and Translational Research (ECTR), Biocon Bristol-Myers Squibb Research and Development Center (BBRC), Bangalore. She started the ECTR department in 2010 and played an instrumental role in setting up the Clinical Biomarkers laboratories at BBRC. Her current research interests involve assay development and qualification of Clinical Biomarkers, especially in Oncology and Immuno-oncology and its use in clinical trials, while collaborating with multiple internal teams and global stakeholders. Her other interests are to pursue exploratory and translational research to understand the underlying mechanisms of cancer. In her additional roles, she also provides leadership in Managing the regulatory paperwork and clinical sample logistics to handle global clinical trial sample shipments for BMS to support the clinical biomarker work. She obtained a PhD in Molecular and Cellular Biology from the Indian Institute of Science, Bangalore and studied DNA-protein interactions to decipher novel transcription activation mechanisms in prokaryotic model systems. She carried out Post-doctoral research from The Salk Institute for Biological Sciences, San Diego and Stanford School of Medicine, Palo Alto. Her research in these two places was focused on understanding the intriguing complexities of cancer signaling pathways. She worked as a Research Scientist in the Veterans Affairs Medical Center (VAMC), San Francisco on multiple projects involving translational research in Cancer. She has published her research work in numerous top peer-reviewed international journals such as Cell, Molecular Cell etc. She has also served as a Reviewer for many American Association of Cancer Research (AACR) Journals like Cancer Research and Clinical Cancer Research and written and obtained international grants.
Abstract:
Biomarkers have many significant applications in oncology, including diagnosis, prognosis, risk assessment, prediction of response to treatment and screening and monitoring progression of the disease. Further, cancer biomarkers play an important role during all phases of drug discovery and development and in guiding early decision in clinical trials. Real-time quantitative polymerase chain reaction (RT-qPCR) technology has become the method of choice for clinical biomarker detection and quantification since it is accurate, sensitive, fast and relatively cheaper than other available gene expression-based technologies. Although a thorough analytical and clinical biomarker assay validation is not required for discovery-phase work, as a drug progresses into preclinical and early-phase clinical studies, it becomes important to have more rigorously qualified biomarkers. A “fit-for purpose” assay development and validation to meet the clinical requirements plays a significant role in cancer biomarker quantification. Development and use of RT-qPCR technology for robust, accurate and reliable method is required for the “fit-for-purpose” biomarker assay qualification. Few important factors influencing assay performance such as sample matrix, sample preparation, experimental precision, reproducibility, sensitivity, specificity, dilution linearity and dynamic range and their impact on the assay outcome will be discussed. Based on these, we will put forth recommendations for consideration and optimization of qPCR-based clinical cancer biomarker assays by demonstrating a few examples. Lastly, a few representative case studies of safety/efficacy and pharmacodynamic cancer biomarkers will be discussed that exemplify enabling of early decision making in Oncology and Immuno-oncology clinical trials.
- Symposium
Location: Sylt 5
Session Introduction
Mohammad O Hoque
Johns Hopkins University, Baltimore, USA
Title: Methylation biomarkers for low grade urothelial cancer (LGUC) management
Biography:
Mohammad O Hoque is an Associate Professor of Otolaryngology-Head & Neck Surgery, Urology and Oncology at Johns Hopkins University School of Medicine. His major research interests includes: a) To understand molecular biologic basis of head and neck, lung and genitourinary cancer b) To develop and validate genetic and epigenetic approach for early cancer diagnosis, cancer risk assessment and cancer prognosis and c) To identify molecular alterations due to environmental exposures such as active smoking, passive smoking and arsenic. He has published over 95 papers in reputed journals and has been serving as an Editor and/or Editorial Board Member of several bio-medical journals.
Abstract:
Over 90% of bladder cancer in the western world present as urothelial carcinoma (UC), from which non-muscle invasive urothelial cancers (NMIBC) is the most common histology at presentation (around 75%). NMIBC is usually treated by trans-urethral resection of bladder tumor (TURBT) where 20% of patients will be cured, 70% will recur at least once every 5 years, and the remaining will progress to muscle-invasive disease with poor prognosis. Currently there are no well validated markers that can discern the tumors at the time of diagnosis that will recur/progress from those that will not. Moreover, conventional approaches are not ideal to predict risk of recurrence/progression. Hence, it is crucial to develop molecular markers that can predict recurrence/progression at the time of diagnosis and such markers will allow a more individualized therapy based on a patient’s risk. Furthermore, it would also be important to develop a test that could provide cost-effective, non-invasive monitoring for low-risk patients, while using a more active approach to identify high-risk cancers before they progress. By a candidate gene approach, we analyzed the promoter methylation (PM) of 8 genes genes (ARF, TIMP3, RAR-β2, NID2, CCNA1, AIM1, CALCA and CCND2) by quantitative methylation specific PCR (QMSP) in DNA of 17 non-recurrent and 19 recurrent noninvasive low grade papillary urothelial carcinoma (LGPUC) archival tissues. Among the genes tested, by establishing an empiric cutoff value, CCND2, CCNA1, NID2, and CALCA showed higher frequency of methylation in recurrent than in non-recurrent LGPUCC: CCND2 10/19 (53%) vs. 2/17 (12%) (p=0.014); CCNA1 11/19 (58%) vs. 4/17 (23.5%) (p=0.048); NID2 13/19 (68%) vs. 3/17 (18%) (p=0.003) and CALCA 10/19 (53%) vs. 4/17 (23.5%) (p=0.097), respectively. We further analyzed PM of CCND2, CCNA1, and CALCA in urine DNA from UC patients including LGPUC and controls. The frequency of CCND2, CCNA1 and CALCA was significantly higher (p<0.0001) in urine of UC cases [38/148 (26%), 50/73 (68%) and 94/148 (63.5%) respectively] than controls [0/56 (0%), 10/60 (17%) and 16/56 (28.5%), respectively)]. Most importantly we found any one of the 3 markers methylation positive in 25 out of 30 (83%) cytology negative LGPUC cases. We also explored the biological function of CCNA1 in UC. Prospective confirmatory studies are needed to develop a reliable tool for prediction of recurrence using primary LGUC tissues and/or urine.
Masamichi Hayashi
Nagoya University School of Medicine, Japan
Title: Molecular surgical margin analysis and postoperative locoregional cancer recurrences
Biography:
Masamichi Hayashi has completed his MD and PhD from Nagoya University, and Post-doctoral studies from Johns Hopkins University School of Medicine. Now he is an Assistant Professor of the Department of Gastroenterological Surgery 2, Nagoya University Hospital. He has published more than 20 papers in reputed journals, and he is also a General Surgeon of the hospital.
Abstract:
Oncologic evaluation of surgical margins has long depended on visible histologic diagnosis. Although intraoperative cytology or frozen section diagnosis directs surgery to be performed in a more adequate way, some histologic negative surgical margins still have genetic or epigenetic alterations associated with disease recurrence. This phenomenon may be partly explained by "field cancerization," which is characterized as the presence of clonally related cells with malignant potential containing one or more cancer-associated genetic or epigenetic alterations in the tumor-surrounding mucosal areas. Another issue linked to recurrence is undetected fully developed residual tumor cells especially at the deep surgical margins. Histologically undetected residual cancer cells may be left behind due to the "tumor budding" phenomenon, defined as a single cancer cell or a cluster of <5 cancer cells protruding into the stroma beyond the invasive front. These are hard to detect in intraoperative frozen samples by light microscopy, which depends on the identification of visible clusters of cells having the malignant phenotype. To overcome the problem, we developed the molecular surgical margin analysis using nitrocellulose sheet which can collect unvisible tiny cancerous cells on the surface of the surgical specimen. We also utilized rapid quantitative methylation specific PCR (QMSP) and digital QMSP. All included surgical samples were histopathologically margin-negative. Our data indicated the association of molecularly positive margin with postoperative locoregional recurrences. We applied the assay to Head and neck squamous cell carcinoma cases, and try to apply it to other gastroenterological cancers.
Inmaculada Ibanez de Caceres
University Hospital La Paz. IdiPAZ, Spain
Title: Predictive DNA methylation markers for platinum response in cancer
Biography:
Inmaculada Ibanez de Caceres has completed her PhD from Complutense University of Madrid, Spain; 6 years of Post-doctoral studies from Fox Chase cancer Center at Philadelphia, and IIB/CSIC, from the National Research Council, Spain. She coordinates the experimental therapies and biomarkers group at The Sanitary Research Institution IdiPAZ, and is the Director of the Cancer Epigenetics Group at University Hospital La Paz, Madrid. She has published more than 30 papers in reputed journals, is the main author of two patents based on biomarkers of clinical use, one of them already licensed and under exploitation, and has been serving as a Full Member representing her institution at the biomarkers platform form the European Infrastructure for Translational Medicine (EATRIS).
Abstract:
One of the major problems associated with the identification of biomarkers for clinical use, is the lack of validation in different cohorts of patients after publication in scientific journals. More than 50,000 manuscripts/year are currently estimated in this field, and only 18 candidates in recent decades have been studied further in clinical trials with cancer patients. Within the cancer markers, the predictive ones are most needed in order to help in the treatment election, as nowadays, the vast majority of tumors are still treated with the same conventional therapy of the last 20 years, characterized by its low specificity, high toxicity and lack of ability to discriminate between patients with different sensitivity. Platinum compounds, are the standard treatment of tumors with high incidence such as lung, ovary and colorectal, so finding markers able to discriminate differential response to its use would allow patient selection and optimizing the use of chemotherapy and associated health spending. My laboratory is focussed in the study of the epigenetic biomarkers that we have identified and published from previous research projects, expanding their use to other validation cohorts of patients with solid tumors treated with platinum, that could eventually benefit from its use. We are also working in the identification of novel biomarkers for therapy response election, first through exosomal content characterization, coming both, from resistant cells and circulating in the serum of cancer patients; and secondly, through the development of platinum-predictive artificial intelligence systems generated by the omics data "in vitro", "in silico" and from the health system patients. We validate our findings through different high sensitivity epigenetic methodologies of routine in the laboratory and establish functional assays to validate in all cases the association with the response to therapy.