Liquid profiling of RNA and DNA for treatment response prediction and monitoring of cancer patients

Christof Winter 1,
1TU München, Germany; 

Cell-free nucleic acids released from dying tumor cells can readily be detected in the blood plasma. To distinguish tumor from normal cell-free nucleic acids, tumor-specific mutations can be used. Here I will present the results of two studies using this liq- uid profiling approach for tumor load monitoring and personalized treatment in cancer patients.
In breast cancer, where the tumor mutation spectrum differs substantially between patients, we make use of individual chro- mosomal rearrangements in the tumor that we detect and quantify in patient blood over time using personalized droplet digital PCR assays. This allowed to retrospectively detect a metastatic recur- rence in blood on average 11 months before clinical detection with symptoms. Early detection and early treatment might lead to improved patient survival.
In prostate cancer, the androgen receptor (AR) is an important target for hormone therapy (androgen deprivation therapy). How- ever, a considerable fraction of tumors expresses a splice variant (AR-V7) that is resistant to hormone therapy. We designed droplet digital PCR assays specific for AR and for AR-V7 and then quan- tified RNA levels of these transcripts in patient whole blood. In patients with metastatic prostate cancer, we found that high AR- V7 blood levels before therapy initiation were associated with poor progression-free survival and poor overall survival under hormone therapy. Notably, we found that none of the patients with high AR-V7 levels did respond to a subsequent hormone therapy. Trans- lating these results into routine clinical testing will contribute to precision oncology.

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