Abstract 2355: Identification of genetic and metabolic impairments to improve chemotherapeutic efficacy

• Published in: Cancer research (Chicago, Ill.) Ill.), 2021-07, Vol.81 (13_Supplement), p.2355-2355
• Main Authors: Freeman, Herman L., Li, Yuan-yuan, McRitchie, Susan L., Pathmasiri, Wimal W., Sumner, Susan J., Mass, Baba B., Nance, Brea C., Voruganti, Saroja, Stewart, Delisha Antionette
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2021-2355

Genetic polymorphisms associated with drug metabolism can significantly impair chemotherapeutic efficacy. Some African American women have poor treatment response to taxane-based chemotherapy drugs, which are widely used to treat breast cancer (BCa). Our study sought to identify gene-metabolite interactions to determine how selected polymorphisms impact treatment-relevant metabolic pathways that may contribute to poor response. This approach will enable more precise treatment based on genetically-defined metabolic drug-response as well as the consideration of ethnicity which can also play a role in disparate cancer outcomes. We treated a panel of four BCa cell lines derived from tumors taken from African American or Caucasian women with paclitaxel, at LD50 ≈ 100 ng/mL, determined by MTT assay across all lines. Cell pellets were collected for three replicate experiments for treated versus untreated conditions and UPLC high resolution mass spectrometry untargeted metabolomics was performed to identify significantly perturbed metabolic pathways that differentiate response to paclitaxel treatment. We observed differentiation between the four cell lines based on the specific metabolites that separated treated versus control/line using supervised multivariate analysis. Further, three endogenous pathways (Benzoate degradation via CoA ligation, Electron transport chain and Nucleotide sugar metabolism) were significantly perturbed (p