Table 2.

Pharmacogenomic challenges to the study of pharmacoethnicity in cancer therapeutics, with potential solutions and ways of advancing investigation

ChallengeSolution
1. Clinical trials of pharmacoethnicity require diverse populations1. (a) International collaborations
(b) Repeat trials in multiple different countries
2. Chemotherapy-related effects are likely to be under multigenic control2. (a) Include multiple mechanism-related and metabolism-related pathways in the same model
(b) Use unbiased, genome-wide models
3. Chemotherapy cannot be administered to healthy volunteers3. Incorporate cell-based models (e.g., HapMap Project)
4. Potentially important polymorphisms may be generally uncommon4. (a) Appropriately power clinical trials
(b) Study ethnic populations enriched for the phenotype of interest
(c) Employ next generation sequencing to discover rare variants
5. Genome-wide associations use multiple-SNP testing, which generates many false-positive SNPs5. (a) Include discovery and replication sets
(b) Validate findings (preclinically and clinically)
(c) Use rigorous statistical methodology