Future paradigms for precision oncology

Giannoula Lakka Klement _, Knarik Arkun, Dalibor Valik, Tina Roffidal, Ali Hashemi, Christos Klement, Paolo Carmassi, Edward Rietman, Ondrej Slaby, Pavel Mazanek, Peter Mudry, Gabor Kovacs, Csongor Kiss, Koen Norga, Dobrin Konstantinov, Nicolas André, Irene Slavc, Henk van Den Berg, Alexandra Kolenova, Leos Kren, Jiri Tuma, Jarmila Skotakova and Jaroslav Sterba

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Oncotarget. 2016; 7:46813-46831. https://doi.org/10.18632/oncotarget.9488

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Giannoula Lakka Klement1,2, Knarik Arkun3, Dalibor Valik4,5, Tina Roffidal1, Ali Hashemi6, Christos Klement6, Paolo Carmassi6, Edward Rietman6,7, Ondrej Slaby4,8, Pavel Mazanek4,5, Peter Mudry4,5, Gabor Kovacs9, Csongor Kiss10, Koen Norga11, Dobrin Konstantinov12, Nicolas André13,14, Irene Slavc15, Henk van Den Berg16, Alexandra Kolenova17, Leos Kren18,19, Jiri Tuma19,20, Jarmila Skotakova8,19 and Jaroslav Sterba4,19,21

1 Department of Pediatric Hematology/Oncology, Floating Hospital for Children at Tufts Medical Center, Boston, MA, USA

2 Department of Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA

3 Department of Pathology, Tufts Medical Center, Boston, MA, US

4 Department of Paediatric Oncology, University Hospital Brno, Brno, Czech Republic

5 Regional Center for Applied Molecular Biology, RECAMO, Brno, Czech Republic

6 CSTS Health Care®, Toronto, Canada

7 Computer Science Department, University of Massachusetts, Amherst, MA, USA

8 Central European Institute of Technology, Masaryk University, Brno, Czech Republic

9 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary

10 Department of Pediatric Hematology-Oncology, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

11 Antwerp University Hospital, Edegem, Belgium

12 Specialized Children’s Oncohematology Hospital, Sofia, Bulgaria

13 Department of Pediatric Hematology and Oncology, AP-HM, Marseille, France

14 UMR S_911 CRO2 Aix Marseille Université, Marseille, France

15 Department of Pediatrics, Medical University of Vienna, Vienna, Austria

16 Department of Pediatric Oncology, Emma Children Hospital Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

17 Department of Pediatric Oncology, Comenius University, Bratislava, Slovakia

18 Department of Pathology, University Hospital Brno, Brno, Czech Republic

19 Faculty of Medicine, Masaryk University, Brno, Czech Republic

20 Department of Pediatric Surgery, University Hospital Brno, Brno, Czech Republic

21 ICRC St. Anna University Hospital Brno, Brno, Czech Republic

Correspondence to:

Giannoula Lakka Klement, email:

Keywords: precision medicine, targeted therapy, genomics, metronomic chemotherapy

Received: December 07, 2015 Accepted: March 31, 2016 Published: May 19, 2016


Research has exposed cancer to be a heterogeneous disease with a high degree of inter-tumoral and intra-tumoral variability. Individual tumors have unique profiles, and these molecular signatures make the use of traditional histology-based treatments problematic. The conventional diagnostic categories, while necessary for care, thwart the use of molecular information for treatment as molecular characteristics cross tissue types.

This is compounded by the struggle to keep abreast the scientific advances made in all fields of science, and by the enormous challenge to organize, cross-reference, and apply molecular data for patient benefit. In order to supplement the site-specific, histology-driven diagnosis with genomic, proteomic and metabolomics information, a paradigm shift in diagnosis and treatment of patients is required.

While most physicians are open and keen to use the emerging data for therapy, even those versed in molecular therapeutics are overwhelmed with the amount of available data. It is not surprising that even though The Human Genome Project was completed thirteen years ago, our patients have not benefited from the information. Physicians cannot, and should not be asked to process the gigabytes of genomic and proteomic information on their own in order to provide patients with safe therapies. The following consensus summary identifies the needed for practice changes, proposes potential solutions to the present crisis of informational overload, suggests ways of providing physicians with the tools necessary for interpreting patient specific molecular profiles, and facilitates the implementation of quantitative precision medicine. It also provides two case studies where this approach has been used.

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