in 2003, preceded personalized medicine, followed by the phase 1 and Hap-Map
projects in 2005 aimed at haplotypic mapping of human genome. The ENCODE
pilot project ensued, i.e., generation of the DNA elements encyclopedia in 2007
(identification and analysis of functional elements in 1 % of the genome). Subse-
quently, DNA sequencing of the genome was carried out with the aim to establish
diversity in 1000 human genomes.^7
The most common perception of genomic medicine is providing information on
an individual risk of developing disease based on obtained genome sequence. These
data should be combined with other -omics methods, data gained by collecting
environmental samples, and data on the lifestyle of the patient. Only one approach,
e.g. genome sequencing, is not sufficient. Genome does not remain stable during
lifetime somatic mutations in different cell types can play the key role in the
development of many different diseases such as cancer, as well as in other poly-
genic diseases. During lifetime, changes can occur at both genomic sequence and
epigenetic level. It is not recommended to confine analysis to only one genomic
sequence and one cell type. Many valuable data can be lost if analysis is restricted
solely to peripheral blood cells, which are most commonly used due to their
availability. For personalized medicine, tissue analysis is more important than
peripheral blood cells, but invasive approach for collecting tissue samples does
not allow the usage of tissues as primary sample source for analysis. For this reason,
it is indispensable to figure out noninvasive methods, minimally invasive methods,
and single cell analyses.^8
Stratified medicine is limited to identification of the patient subgroups with
particular diagnosis that respond to a specific treatment, and therefore it represents
only one but important element of personalized medicine, as evidenced by a few
examples of its current clinical application, including the drugs gefitinib and
erlotinib used to treat nonsmall cell carcinoma patients bearing the mutation in
EGF-Rgene or vemurafenib designed for treating metastatic melanoma patients
with the V600 mutation inBRAFgene.^9
Third and most commonly used synonym for personalized medicine is precise or
-omics-based medicine that points to specific elements underlying pathology of a
particular subject at a single point in time. Simply, it means getting the right drug to
the right patient at the right time. This term encompasses stratification tools and
takes into account a huge number of diverse factors that can impact disease
development in a particular subject (not only genomic and biological but also
environmental factors and lifestyle as well) and efficiently predicts disease (pre-
ventive medicine). In summary, personalized medicine should be perceived as a
whole, genomic, layered, and precision medicine involving four proactive princi-
ples. It also implies the transfer or responsibility from medical personnel to
individual subjects (excluding old and helpless subjects and infants).^10
(^7) Goldstein et al. ( 2003 ).
(^8) Aspinall and Hamermesh ( 2007 ), Goldstein et al. ( 2003 ), and Van’t Veer and Bernards ( 2008 ).
(^9) Clark et al. ( 2006 ).
(^10) ESF Forward Look ( 2012 ), Bosˇnjak et al. ( 2008 ), Petricoin et al. ( 2002 ), and Li et al. ( 2008 ).
4 K. Pavelic ́et al.