Personalized_Medicine_A_New_Medical_and_Social_Challenge

(Barré) #1

Personalized medicine is based on an individual approach to the patient in terms of
diagnostics and therapy. It is a paradigm that every physician has encountered
during his or her medical education, but the implementation of personalized
medicine in clinical practice has always been limited in several aspects. Physical
examination, simple laboratory tests, and conventional radiology were the only
available diagnostic tools for many decades. It was not a favorable setting to tailor
diagnostics and therapy in accordance with specific patient’s needs. Strong tech-
nological and scientific impact, along with permanent implementation of new
medical insights, has substantially improved our capabilities. Genetic and molec-
ular diagnostics and interventions are prerequisites to step deeper into this thrilling
area. The term pharmacogenomics refers to the science of how genes and expres-
sion of genes determine drug behavior.^1 This principle is emerging as a major
strategy in new drug discovery and development. The role of imaging would be the
detection of specific receptors for diagnosis and treatment monitoring. The quin-
tessence of personalized medicine is treatment strategies that combine diagnostic
testing with targeted therapy (theranostics).^2 A good example is the usage of human
epidermal growth factor receptor 2 (HER2) testing of tissue specimen before the
administration of trastuzumab. HER2 is a member of the epidermal growth factor
receptor (EGFR) family. HER2 overexpression is correlated with aggressive tumor
behavior and poor clinical outcome. Therefore, HER2 has become an important
prognostic and predictive factor, as well as a target for molecular therapies.^3 In
breast cancer, overexpression of HER2 correlates with response to trastuzumab, an
antibody targeting the HER2 protein.^4 Breast cancer cells overexpressing HER2 are
dependent on the growth stimulatory signals originating from HER2, and blocking
HER2 signaling by trastuzumab inhibits proliferation and causes apoptosis. In the
absence of HER2 overexpression, trastuzumab is ineffective. Although molecular
characterization of the tumor tissue can help guide the treatment, we have to bear in
mind that HER2-positive breast cancer is a heterogeneous disease, and possible
discordance in HER2 status between primary tumors and distant metastases^5 might
lead to unpredictable long-term responses to anti-HER2 therapy and to a variable
outcome.^6 Obtaining consistent imaging data on HER2 expression, both in primary
lesions and in distant metastases, and the elimination of laborious testing pro-
cedures affable to errors and bias, may reduce the number of false-negative or
false-positive results from the currently used ex vivo methods. Several noninvasive
imaging techniques, including positron emission tomography with computed
tomography (PET/CT), single photon emission computed tomography (SPECT),
magnetic resonance imaging (MRI), and optical imaging, have demonstrated


(^1) Evans and Johnson ( 2001 ), Hoehe et al. ( 2003 ), and Terra and Johnson ( 2002 ).
(^2) Kelkar and Reineke ( 2011 ).
(^3) Citri and Yarden ( 2006 ).
(^4) Vogel et al. ( 2002 ).
(^5) Santinelli et al. ( 2008 ) and Krawczyk et al. ( 2009 ).
(^6) Vanden Bempt et al. ( 2007 ).
220 D. Miletic ́et al.

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