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Table 5 Selected cases of aberrant PK or target expression likely affecting administered therapies

From: The impact of pharmacokinetic gene profiles across human cancers

Ctype

Patient

Primary regimen

Additional therapy

Age

Stage

Grade

Detailsa

Target c

Metabolism

Transport

BRCA

TCGA-E2-A1LB

Cyclo-phosphamide Paclitaxel Doxorubicin Anti-Hormoneb

Trastuzumab

41

2

–

ER-

 

AKR1A1(3.01) - Dox

ABCC2(4.77) - Pac

BRCA

TCGA-E2-A158

–

43

2

–

ER-

MAP2(−3.56) - Pac MAP4(− 3.29) - Pac

 

ABCC1(2.27) - Dox

BRCA

TCGA-E2-A14V

Lapatinib

53

2

–

ER+

EGFR(−4.65) - Lap

CYP2C8(2.2) - Pac

 

BRCA

TCGA-AO-A0J3

Fluorouracil Methotrexate

67

2

–

ER+

MAP4(−3.11) - Pac

 

ABCC5(2.21) - 5FU,Meth FOLR1(− 3.42) - Meth

BRCA

TCGA-BH-A0BA

–

51

3

–

ER+

 

NQO1(3.22) - Dox

ABCC2(3.09) - Pac

BRCA

TCGA-AO-A0JE

Trastuzumab

53

3

–

ER-Margin+

  

ABCC1(2.73) - Pac, Dox ABCC2(3.86) - Pac, Dox

OV

TCGA-09-0367

Carboplatin Doc/Paclitaxel

Gemcitabine

67

3

3

LI + TRD+

MAP2(−3.66) - Pac MAP4(−3.96) - Pac

NT5C(3.78) - Gem

SLC31A1(−2.67) - Car

OV

TCGA-23-1123

Doxorubicin

59

3

3

LI + TRD+

 

NR1I2(3.42) - Pac

RALBP1(4.17) - Car,Dox

OV

TCGA-24-1558

Doxorubicin

73

3

3

TRD+

MAP2(−4.71) - Pac,Doc

 

ABCC1(6.49) - Gem,Dox AABCC10(2.66) - Gem,Dox

OV

TCGA-30-1860

Doxorubicin

58

3

3

TRD+

TOP2B(−4.39) - Pac,Dox MAP2(− 5.04) - Pac,Dox

  

OV

TCGA-61-1724

Doxorubicin Gemcitabine

47

3

3

LI+

MAP2(−4.57) - Doc

DCTD(4.46) - Gem

 

OV

TCGA-61-1741

Tamoxifen

76

3

3

TRD+

 

CYP2C8(3.19) - Pac,Tam NR1I2(3.94) - Pac,Tam

SLC31A1(−3.21) - Car

KIRC

TCGA-CJ-4638

Gemcitabine Fluorouracil

Bevacizumab

46

4

4

–

 

NT5C(3.84) UPB1(3.87) DPYS(2.33) - Gem,5FU

 

LUAD

TCGA-50-5072

Doc/Paclitaxel Carbo/Cisplatin

 

74

3

–

reformed smoker

  

ABCC2(5.12) - Doc,Pac

UCEC

TCGA-AP-A052

Carboplatin Paclitaxel

Gemcitabine

59

4

3

 

CMPK1(−4.12) - Gem

NR1I2(3.92) - Pac

 

UCEC

TCGA-AP-A05D

 

67

3

3

 

MAPT(−3.05) - Pac TUBB1 (−2.43) - Pac

 

SLC31A1(− 3.7) - Carb

UCEC

TCGA-AP-A0LI

 

67

3

3

 

MAP2(−5.57) - Pac MAPT(−2.21) - Pac

 

SLC31A1(−4.11) - Carb

UCEC

TCGA-AX-A0IS

Gemcitabine Brivanib

52

1

2

 

MAP2(−3.09) - Pac MAP4(− 3.27) - Pac

DCTD(3.49) - Gem

 

UCEC

TCGA-AX-A1CR

 

70

2

3

  

NR1I2(3.18) - Pac

SLC31A1(−5.04) - Carb

UCEC

TCGA-BS-A0TE

Doxorubicin Topotecan

35

4

3

  

AKR1C3(4.88) NQO1(3.68) NR2I1 (2.76) - Dox,Pac

ABCC2(5.22) - Top

HNSC

TCGA-CR-7404

Carboplatin Paclitaxel

Cepecitabine Cetuximab

53

1

–

never smoker

MAP2(−3.86) - Pac

 

ABCC5(5.08) - Cap

HNSC

TCGA-DQ-7589

Docetaxel Fluorouracil

70

1

–

reformed smoker

  

ABCC1(5.83) - Doc,5FU,Pac ABCC5(4,74) - Coc,5FU,Pac

LUSC

TCGA-46-6026

Doc/Pacletaxel

Gemcitabine Paraplatin

81

2

–

reformed smoker

CMPK1(−3.05) - Gem

CYP2C8(3.02) - Pac NR1I2(3.86) - Pac

 

LUSC

TCGA-94-7033

Cisplatin

73

1

–

reformed smoker

MAP4(−4.71) - Doc

 

SLC31A1(−3.26) - Cis

  1. aSpecific details for each case: ER, estrogen receptor; Margin, presence of tumor cells in surgical margins; TRD, rumor residual disease; LI, lymphatic invasion
  2. bAnti-hormone therapies; three received anastrazole, one tamoxifen
  3. cWhen multiple targets are lowly expressed, representatives are shown for brevity
  4. Target or PK genes of drugs for the administered regimen that exhibit differences from normal-tissue expression levels are shown with their Z-scores. After the Z-score, we indicate which administered therapy is directly affected by the expression change using abbreviated names
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BMC Cancer

ISSN: 1471-2407

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