Research

Paclitaxel is one of the most effective and common chemotherapeutic agents used in patients with high risk breast cancer. Patients are treated with standard regimens that are adjusted only for toxicity, which is most often peripheral neuropathy. The primary objective of this project is to discover patient-specific predictors of paclitaxel-induced neuropathy that can be used to develop strategies for dose optimization prior to and during treatment. Secondary objectives of this project are to create an iPhone app that can detect chemotherapy-induced neuropathy and improve communication between patients and their doctors regarding treatment-related neuropathy to ensure that treatment decisions are made based on the individual patient’s therapeutic priorities. 

Tamoxifen is a highly effective hormonal drug used in patients with estrogen receptor positive breast cancer. Tamoxifen is believed to be a prodrug that requires CYP-mediated metabolic activation to endoxifen. The objective of this project is to develop a predictive algorithm that integrates clinical and genetic information to select an ideal tamoxifen starting dose to achieve optimal systemic endoxifen concentration.

Aromatase inhibitors are a newer class of hormonal agents used primarily in post-menopausal patients with estrogen receptor positive breast cancer. We are performing retrospective correlative analyses to discover clinical and genetic predictors of drug concentration, treatment response, and therapeutic outcomes. These genetic analyses utilize a variety of approaches ranging from candidate and genome-wide genotyping to candidate gene sequencing. The ultimate objective is to discover clinically useful predictors that can inform individualized treatment decisions to optimize therapeutic outcomes.  

Drug drug interactions (DDI) can cause treatment to be toxic or ineffective, and in clinical trial subjects can interfere with accurate assessment of the benefits and harms of study agents. We are developing a DDI screening tool to be used during clinical trial eligibility assessment to decrease the prevalence of DDI and enhance patient safety and trial data validity. 

One of the major challenges to clinical implementation of pharmacogenetics has been the additional cost of genotyping with unclear benefit to the individual patient. Patients receiving cancer treatment at the Univeristy of Michigan Rogel Cancer Center may have existing genetic information from a variety of sources, including participation in other research activities. The objective of this project is to use this existing patient genetic information to implement pharmacogenetic-guided personalized medicine. Our primary focus is to demonstrate the viability of this strategy by using existing DPYD informaiton to guide personalized dosing of 5-FU and capecitabine.  

Genetic testing of DPYD prior to fluoropyrimidine chemotherpy has been demonstrated to reduce severe toxicity and healthcare costs. This strategy is standard practice in Europe but not in USA. The objective of this project is to increase the clinical uptake of pre-treatment DPYD testing through research, education, and advocacy. Among the ongoing projects is an analysis of the actiivty of uncommon DPYD variants using a large cohort of patients with known DPYD genotype at University of Michigan.