Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

146 Applying Pharmacogenomics in Therapeutics
Morphometric
Body size
Body composition
Demographic
Age
Race/ethnicity
Sex
Pharmacogenomic
Drug metabolism
Drug transporters
Drug targets
Pharmacokinetics
Absorption
Metabolism
Distribution
Transport
Excretion
Pharmacodynamics
Receptors
Ion channel
Enzymes
Pharmacologic
Dose and schedule
Dosage form
Drug–drug interaction
Drug–complementary and alternative
medicine interactions
Drug–formulation interactions
Drug–food interactions
Physio-pathophysiologic
Disease
Hepatic function
Renal function
Pregnancy
Clinical outcomes
Response
Toxicity
FIGURE 6.1 Factors that may affect drugs’ efficacy and toxicities. (Adapted from Feng X,
et al., US Pharmacist, 37(1), 2–7, 2012. With permission from U.S. Pharmacist/Jobson
Medical Information LLC.)
PGx BIOMARKERS FOR TOXICITIES ASSOCIATED
WITH CANCER THERAPY
Cutting-edge pharmacogenetic research plays an essential role in identifying these
biomarkers that are critical for personalized medicine and enable clinicians to minimize
the risk of “one-size-fits-all” or “trial and error” patient care approaches. Since
the US FDA approved the first pharmacogenetic test (AmpliChip CYP450 Test,
Roche Diagnostics; www.roche.com) in 2004 to identify a patient’s CYP2D6 and
CYP2C19 genotype by analyzing DNA extracted from a whole blood sample, there
are currently over 30 cancer treatment agents with recommended genetic testing.
Based on the clinical evidence, the pharmacogenetic testing is usually mandatory for
those cancer drugs with boxed warning or contraindication for specific genetic polymorphisms.
Some of the pharmacogenetic testing is usually recommended, which
is either clearly recommended or identified at the section “Indications and Usages”
of drug package insert. In addition, some PGx instructions are placed at other sections
of the package insert. 7–8 The clinical recommendations for PGx associated
with cancer treatments are also publicly available from clinical guidelines published
by the Clinical Pharmacogenetics Implementation Consortium (CPIC), National
Comprehensive Cancer Network (NCCN), and American Society of Clinical
Oncology (ASCO). Table 6.1 lists some key biomarkers commonly associated with