Some treatments for prostate cancer, while initially effective at controlling the disease, not only stop working after a certain period of time but actually start driving tumor growth.

Complex genetic analysis of biopsies and blood samples from patients with advanced prostate cancer shows that treatments can act as an evolutionary force on the population of cancer cells in a tumor.

Scientists the Institute of Cancer Research (London, UK) and their international colleagues studied the dynamics of common genomic aberrations in sequential plasma and tumor samples from V-ets avian erythroblastosis virus E26 oncogene homolog (ERG)-positive castration-resistant prostate cancer CRPC patients who received treatment with abiraterone. Archived formalin-fixed paraffin-embedded (FFPE) blocks were obtained from pathology archives.

Buccal swab and FFPE DNA were extracted and circulating DNA was extracted from plasma with the SnoMag Circulating DNA kit (Snova Biotechnologies; Warren, NJ, USA) and libraries were sequenced on the Ion Torrent Personal Genome Machine (PGM) (Life Technologies; Grand Island, NY, USA). Genotypes of study single nucleotide polymorphisms (SNPs) were determined from the germ-line samples to compile the list of informative SNPs for each patient. Point mutations for tumor samples were identified by applying strict filtering procedures on coverage, allelic fraction, and genomic position.

The team concentrated in particular for clues that glucocorticoids could favor the survival of cells containing androgen receptor mutations, affecting how cells respond to hormones. They used repeat biopsies from tumors and analyzed circulating tumor DNA over time, monitoring the emergence of cancer cell clones containing each mutation. In several patients, the use of glucocorticoids coincided with the emergence of androgen receptor mutations and the progression of cancer into more advanced forms. The study also showed that measuring circulating tumor DNA levels, which is less expensive and invasive than taking repeated samples of tumors with needle biopsies, could be used to monitor the emergence of treatment-resistant prostate cancer.

Gerhardt Attard, MD, PhD, a Clinician Scientist and a senior author of the study said, “Our study showed that a steroid treatment given to patients with advanced prostate cancer—and often initially very effective—started to activate harmful mutations and coincided with the cancer starting to grow again. In the future, we hope to routinely monitor genetic mutations in patients with advanced disease using just a blood test, enabling us to stop treatments when they become disease drivers and select the next best treatment option.” The study was published on September 17, 2014, in the journal Science Translational Medicine.

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