Cancer pharmacogenomics, challenges in implementation, and patient-focused perspectives

Figures & data

Figure 1 Summary of somatic cancer biomarkers and targeted therapies.

Notes: This figure depicts examples of key signaling pathways and downstream effects of mutations within somatic biomarkers, and their respective targeted therapies.
Abbreviations: ALK, anaplastic lymphoma kinase; JAK, Janus kinase; mTOR, mammalian target of rapamycin; p13K, phosphoinositide 3-kinase; TDM-l, ado-trastuzumab emtansine; VEGFR, vascular endothelial growth factor receptor.

Table 1 Summary of oncology pharmacogenomic biomarkers in FDA drug labeling

Disease	Biomarker	Therapy	Frequency
Breast	HER2	Trastuzumab, lapatinib, pertuzumab, ado-trastuzumab emtansine	20%
	ESR1	Exemestane, letrozole, anastrozole, fulvestrant, tamoxifen,	60%
Colorectal	KRAS	Cetuximab, panitumumab	35%–40%
	EGFR	Cetuximab, panitumumab	35%–45%
	DPYD	5-Fluorouracil, capecitabine	<5%
	UGT1A1	Irinotecan	30%
Lung	ALK	Crizotinib, ceritinib	5%–7%
	EGFR	Erlotinib, gefitinib, afatinib, osimertinib	15%–20%
Melanoma	BRAF	Vemurafenib, dabrafenib, trametinib	50%–60%
Acute promyelocytic leukemia	PML-RARα	Arsenic trioxide, tretinion	>95%
Chronic myeloid leukemia	BCR-ABL	Imatinib, dasatinib, nilotinib, bosutinib, ponatinib, omacetaxine mepesuccinate	>95%
	UGT1A1	Nilotinib	30%
Cutaneous T-cell lymphoma	CD-25/IL2RA	Denileukin diftitox	75%
Chronic lymphocytic leukemia (CLL)	del(17p)	Ibrutinib	3%–8% at diagnosis; up to 30% in refractory CLL
	CD20/MS4A1	Obinutuzumab, rituximab	25%
Acute lymphocytic leukemia	TPMT	6-Mercaptopurine, thioguanine	<5%
Non-Hodgkin’s lymphoma	CD20/MS4A1	Rituximab, tositumomab	>90%

Note: Data from http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm.⁸⁷

Abbreviations: DPYD, dihydropyrimidine dehydrogenase; UGT1A1, uridinediphosphate glucuronosyl transferase 1A1; ALK, anaplastic lymphoma kinase; CD, cluster of differentiation; del(17p), deletion 17p; TPMT, thiopurine-S-methyltransferase; FDA, Food and Drug Administration.

Table of Pharmacogenomic Biomarkers in Drug Labeling [webpage on the Internet]Silver Spring, MDUS Food and Drug Administration2015 Available from: http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htmAccessed May 5, 2016

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