Harnessing pharmacological knowledge for personalized medicine and pharmacotyping: Challenges and lessons learned

Table 1 Genes used as predictive pharmacogenomics biomarkers to assess the safety and efficacy clinical profiles of individual marketed anticancer drugs^1,2

Drug	Gene	Safety/efficacy profile
Anastozole	ER	Lower efficacy; no response in cancer patients with tumor ER-negative expression
Capecitabine	DPYD	Lower safety; ADRs; Orodigestive neutropenia
Cetuximab	EGFR	Lower efficacy; no response in cancer patients with tumor EGFR-negative expression
	K-RAS	Lower efficacy; no response in cancer patients with tumor specific K-RAS mutations
Cisplatin	TPMT	Lower safety; ADRs; cytotoxicity associated with hearing loss in children
Crizotinib	ALK	Efficacy; indication only in patients bearing ALK gene rearrangement positive tumors (EML4-ALK translocation)
Dabrafenib	BRAF	Efficacy; indicated only in melanoma patients with BRAF V600E mutation
	G6PD	Safety; ADRs; toxicity in G6PD deficient patients
Dasatinib	Ph+	Efficacy; indicated only for Ph+ tumors
Erlotinib	EGFR	Lower efficacy; no response in cancer patients with tumor EGFR-negative expression
Everolimus	Her2/Neu	Efficacy; indicated in HER2 protein overexpression negative in breast cancer women
	ER	Efficacy; indicated for breast cancer women bearing ER positive tumors (ESR1+)
Exemestane	ER	Lower efficacy; no response in cancer patients with tumor ER-negative expression
Imatinib	Ph+	Efficacy; indicated only for Ph+ tumors
	PDGFR	Efficacy; indicated in myelodysplastic- myeloproliferative syndromes with PGFRR gene rearrangements
	FIP1L1-PDGFRA	Efficacy; assessment of FIP1L1-PDGFRA translocation -fusion kinase in tumors
	c-kit	Lower efficacy; no response in cancer patients with absence of tumor activating c-Kit mutations
Irinotecan	UGT1A1	Lower safety; ADRs; diarrhea, increased risk for severe neutropenia in high doses of irinotecan
Lapatinib	Her2/Neu	Efficacy; indicated for over-expressing Her2/Neu advanced or metastatic breast cancer
Letrozole	ER	Lower efficacy; no response in cancer patients with tumor ER-negative expression
Nilotinib	Ph+	Efficacy; indicated only for Ph+ tumors
	UGT1A1	Safety; increased risk of hyperbilirubinemia in patients with UGT1A1*28 genotype
6-Mercaptopurine	TPMT	Lower safety; ADRs; neutropenia
Panitumumab	EGFR	Lower efficacy; no response in cancer patients with tumor EGFR-negative expression
	K-RAS	Lower efficacy; no response in cancer patients with tumor specific K-RAS mutations
Pertuzumab	HER2/Neu	Efficacy; indicated only for HER2/Neu+ breast cancer
Tamoxifen	ER	Lower efficacy; no response in cancer patients with tumor ER-negative expression
	CYP2D6	Lower efficacy; loss of therapeutic benefit for PMs and/or upon co-administration with CYP2D6 inhibitors; lower plasma levels of active metabolite endoxifen achieved
	FV	Safety; ADRs; risk for venous thromboembolism in breast cancer women also bearing factor V Leiden (FLV) mutations
	F2	Safety; ADRs; risk for venous thromboembolism in breast cancer women also bearing factor II (prothrombin) mutations
Thioguanine	TPMT	Lower safety; ADRs; Neutropenia
Trastuzumab	HER2/Neu	Lower efficacy; no response in cancer patients with tumor HER2/Neu-negative expression
Vemurafenib	BRAF	Efficacy; indicated only in melanoma patients whose tumors has a mutation at amino acid 600 of the B-raf protein (V600E and/or V600K BRAF mutations)

¹See also the table of PGx biomarkers in drug labeling at the FDA that can be accessed at: http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm (Accessed on June 27, 2014); ²Additional data can be seen in “The Pharmacogenomics Knowledge Base (PharmGKB) at: https://http://www.pharmgkb.org/ (Accessed on June 29, 2013). ADRs: Adverse drug reactions; G6PD: Glucose-6-phosphate dehydrogenase deficiency; PM: Poor metabolizers: ER: Estrogen receptor; TMTP: Thiopurine methyltransferase gene; DPYD: Dihydropyrimidine dehydrogenase gene; Ph: Philadelphia chromosome; FV: Factor V; F2: Factor II (prothrombin).