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

150 Applying Pharmacogenomics in Therapeutics
TABLE 6.2 (Continued)
PGx Biomarkers for the Prevention of Toxicity in Cancer Therapy
PGx
Biomarkers Therapeutic Agents PK/PD Impact
CYP2D6 14–16 Tamoxifen Tamoxifen is converted to
the potent active
metabolite endoxifen.
GST1 17 Cyclophosphamide, busulfan A family of enzyme
detoxifying electrophilic
group of some
chemotherapeutic agents.
ERCC1 and Cisplatin, carboplatin,
ERCC2 18 oxaliplatin
ABCB1 (also
known as
MDR1),
ABCB2
ERCC1 is an endonuclease
repairing damaged DNA
segments.
responsible for efflux of
drugs from the cell.
(MRP2) 19 Paclitaxel P-glycoprotein is
Frequency of Affected
Phenotype Clinical Significance
PMs causing absent CYP2D6
activity are found in 7% of
whites, less than 3% of black
Americans and 1% of Asians.
About 57% of white and 13% of
black Americans have deficient
enzyme.
Deficiency of CYP2D6 causes a reduction
in plasma endoxifen levels and may
change toxicity; however, routine
genotyping is not recommended due to
variability.
Deficiency of this enzyme may result in
enhanced drug toxicity.
No data Not conclusive and high gene expression
associated with inferior outcomes for
bladder, gastric, and colorectal cancers.
Three common SNPs have been
identified with ABCB1.
Overexpression of ABCB1 leads to drug
resistance, and patients with wild type
demonstrate reduced neuropathy.
Source: Adapted from Feng X, et al., US Pharmacist, 37(1), 2–7, 2012. With permission.
Note: DPD, dihydropyrimidine dehydrogenase; ERCC1, excision repair cross complementing rodent repair; GST, glutathione S-transferase; TPMT, thiopurine
methyltransferase; UGT, UDP-glucuronyltransferase.