Andrew J. Armstrong, MD, discusses the use of circulating tumor cell to detect chromosomal instability in men with metastatic castration-resistant prostate cancer.
Andrew J. Armstrong, MD, professor of medicine, associate professor in pharmacology and cancer biology, and professor in surgery at Duke University School of Medicine, and member of the Duke Cancer Institute, discusses the use of circulating tumor cell (CTC) to detect chromosomal instability in men with metastatic castration-resistant prostate cancer (mCRPC).
Other mechanisms of resistance to hormonal therapy in prostate cancer exist beyond AR-V7, says Armstrong. One such biomarker is chromosomal instability. Homologous repair deficiencies are becoming increasingly recognized as playing an important role in the development of resistance, but more importantly, in the prediction of response to PARP inhibitors and DNA repair—damaging agents, such as cisplatin or carboplatin, says Armstrong.
In collaboration with Epic Sciences, Armstrong’s team developed an assay that can detect the phenotype of circulating tumor cells that harbor DNA repair defects. Patients with DNA repair defects often have many chromosomal aberrations across the genome, and the cells associated with chromosomal defects have identifiable shapes and sizes, explains Armstrong.
The Epic Sciences platform uses software, similar to facial recognition technology, to detect those cells. Test results revealing high chromosomal instability is associated with a very poor outcome in these patients, says Armstrong. This was prospectively validated in the PROPHECY study in men treated with abiraterone acetate (Zytiga) or enzalutamide (Xtandi). Patients with high chromosomal instability who were treated with either of those agents experienced very short, very poor responses, progression-free survival, and overall survival, concludes Armstrong.