Curators' Favorite Papers

The first of two papers selected for the November edition of ”Curators' Favorite Papers" is from Nature Reviews Genetics (“Prioritizing diversity in human genomics research”). It highlights the necessity of including individuals from diverse backgrounds in genomic research, both as subjects and as researchers. The authors discuss several proposals to achieve these goals beginning with awareness of genetic and environmental factors that contribute to disparities in health outcomes, establishing sources of dedicated funding, recruiting subjects, researchers and clinicians from diverse backgrounds, and the integration of genomics into existing healthcare systems in underserved communities. The authors mention two pharmacogenomic (PGx) examples to remark on the importance of genetic and geographic diversity for clinical genomics: the risk of Stevens-Johnsons Syndrome/ toxic epidermal necrolysis in individuals of Asian ancestry who carry the HLA-B*15:02 allele that are administered carbamazepine as well as the risk of hemolysis in African-American males harboring G6PD alleles that are administered quinine. 

According to a new paper from the journal Oncotarget (“Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: NCI clinical trials planning meeting report on identifying key genes and molecular pathways for targeted endometrial cancer trials.”), metastatic endometrial cancer (EC) is the fourth most common cancer affecting women, with increased incidence and relatively poor prognosis but no new treatments have been approved in approximately two decades. The paper summarizes the findings from a recent meeting of Gynecologic Cancer Steering Committee (GCSC) and the National Cancer Institute (NCI). Experts gathered to review the literature and generate reports to design early phase clinical trials based on molecular pathway research in EC to improve treatment outcomes in women with EC. The authors generated reports for therapies targeting mutations in those pathways that are commonly implicated in a variety of cancers including DNA-damage repair and cell-cycle checkpoint pathways including ERBB2/HER2, PI3K/ATK/mTOR, WNT pathways as well as the dysregulation of those pathways involving ubiquitin-ligase complex, the immune system and metabolic disorders. 

You can read more about HLA-B and carbamazepine, G6PD and quinine, ERBB2/HER2 and other targeted cancer therapies at the Cancer Pharmacogenomics portal on PharmGKB and CPIC.