Textbook of Personalized Medicine - Second Edition [2015]

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these complex multifactorial situations to obtain individual genotypic and gene
expression information. These same tools are applicable to study the diversity of
drug effects in different populations. Pharmacogenomics promises to enable the
development of safer and more effective drugs by helping to design clinical trials
such that non-responders would be eliminated from the patient population and take
the guesswork out of prescribing medications. It will also ensure that the right drug
is given to the right person from the start. In clinical practice, doctors could test
patients for specifi c SNPs known to be associated with non-therapeutic drug effects

Table 5.1 Role of pharmacogenomics in variable therapy targets

Variable target Therapy/prevention Disease
AlloMap® gene profi le Immunosuppressive drugs Heart transplant rejection
Alpha-adducin ACE inhibitors Hypertension
BCR-abl; c-KIT Gleevec/Imatinib Cancer/CML
BRCA1/2 Surveillance; tamoxifen; prophylactic
surgery

Breast and ovarian cancer

CETP HMG-CoA reductase inhibitors Atherosclerosis
CYP2C9/VKORC1 Warfarin Coagulation disorders
CYP2D6/2D19
(Amplichip®)

~25 % of prescribed drugs Drug metabolism in
disease
EGFR Tarceva, Iressa Lung cancer
Estrogen receptor Tamoxifen Breast cancer
Familion® 5-gene profi le Pharma/lifestyle prevention Cardiac rhythm
abnormalities
HER-2/neu receptor Herceptin/Trastuzumab Breast cancer
KRAS mutation Tyrosine kinase inhibitors Lung cancer drug
resistance
MammaPrint 70-gene
profi le

Aduvant chemotherapy Breast cancer recurrence

Oncotype DX: 16 gene
profi le

Chemotherapy protocols Breast cancer recurrence

OncoVue® (117 loci) Surveillance Sporadic breast cancer
p16 gene/CDKN2A Surveillance Melanoma
PML-RAR alpha Tretinoin/all trans retinoic acid Acute myelocytic
leukemia
Sprycel (dasatinib) BCR-Abl Gleevec resistance
TPMT Mercaptopurine Acute lymphocytic
leukemia
Transcriptional profi les Chemotherapy protocols Non-Hodgkin’s lymphoma
Transcriptional profi les Chemotherapy protocols Acute myelocytic
leukemia
TruGene®-HIV 1
genotyping

Antiretroviral drugs HIV virus drug resistance

UGT1A1 Camptosar® (irinotecan) Colon cancer
© Jain PharmaBiotech

5 Pharmacogenomics