The 3rd ACTC Advances in Circulating Tumor Cells Conference was held in Rhodes, Greece October 4-7, 2017. This idyllic island setting off the coast of Turkey provided a relaxed and welcoming atmosphere for discussing the latest advances in cancer and circulating tumor cell research. Talks were divided into 6 plenary lecture sessions consisting of: (1) Recent Advances in the Biology of Metastasis, (2) Liquid Biopsy in Breast Cancer: The Clinician’s Point of View, (3) Liquid Biopsy in Solid Cancers, (4) Recent Advances on the Isolation, Enumeration and Molecular Characterization of CTCs, (5) Circulating Tumor DNA adn Exosomes in Clinical Practice and (6) Future Challenges in Liquid Biopsies. At the end of the meetings, attendees were treated to a tour of the old town, a UNESCO World Heritage Site and preserved medieval settlement with breathtaking views of the Aegean Sea.
One of the standout presentations on the first day of the meeting was given by Dr. Danny Welch, University of Kansas Medical Center, entitled Contributions of Mitochondrial DNA to Metastatic Efficiency. Recent studies have reported that mtDNA mutations can affect the growth and metastasis of tumor cells significantly. Using engineered MNX (mitochondrial-nuclear exchange) mice derived by removing the nucleus from a fertilized egg and inserting an alternative nucleus, Welch could examine mitochondrial effects on mammary cancer using mice that contained identical nuclei (FVB/NJ nuclear DNA) but different mitochondria (either FVB/NJ, C57BL/6J or BALB/cJ mtDNA). His findings demonstrated that MNX mice containing FVB/NJ mitochondria could change or selectively alter nuclear DNA methylation, and these mice were associated with a 3-5-fold increase in metastases. He concluded that mitochondria modulate metastasis and that mtDNA polymorphism inheritance affects tumorigenicity and metastatic efficiency in an oncogenic driver-dependent manner (1,2).
On the 3rd day of the conference, Dr. Siegfried Hauch, Director of CTC Research and Development at QIAGEN, presented a talk entitled Tools for CTC Research in Prostate Cancer: The AdnaPanel Prostate AR-V7. Dr. Hauch discussed a newly developed kit for harvesting and analyzing CTCs which express androgen receptor splice variant-7 (AR-V7). Recent studies have determined that AR-V7 mRNA expression in CTCs is associated with poorer outcomes for men with castration-resistant prostate cancer who receive enzalutamide or abiraterone therapy, but not taxane chemotherapies (3,4). The ability to differentiate AR-V7+ individuals would prove helpful for determining course of treatment. The new AdnaPanel Prostate Cancer AR-V7 involves two steps. In the first step, CTC enrichment is accomplished using the Combination of Combinations Principle (COCP), in which magnetic beads coated with multiple antibodies directed against prostate cancer biomarkers are used to harvest CTCs in a blood sample. Harvested CTCs are then lysed and reverse transcribed to produce cDNA used for multiplex qPCR amplification and detection of CD45, GAPDH, PSA, PSMA, ARwt and AR-V7. A 95% recovery rate was obtained for detecting two tumor cells spiked into 5 ml of healthy donor blood, and positive gene detection was observed down to two LNCap95 cells spiked into 5 ml blood from healthy donors. The developed test panel is designed for researchers who need to perform validated, reproducible, robust and quality controlled CTC testing for AR-V7-related prostate cancer. The AdnaPanel Prostate Cancer AR-V7 Kit is expected to be available in Spring 2018.
For more information on CTCs and CTC-related technologies, check out the following:
- – CTC enrichment and analysis technologies: AdnaTest Select/Detect Kits
- 1. Brinker, A.E. et al. (2017) Mitochondrial haplotype alters mammary cancer tumorigenicity and metastasis in an oncogenic driver-dependent manner. Cancer Res. 77, 6941-6949. (Link)
- 2. Vivian, C.J. et al. (2017) Mitochondrial genomic backgrounds affect nuclear DNA methylation and gene expression. Cancer Res. 77, 6202-6214. (Link)
- 3. Antonrakis, E.S. et al. (2017) Clinical significance of androgen receptor splice variant-7 mRNA detection in circulating tumor cells of men with metastatic castration-resistant prostate cancer treated with first- and second-line abiraterone and enzalutamide. J. Clin. Oncol. 35, 2149-2156. (Link)
- 4. Nakazawa, M. et al. (2015) Serial blood-based analysis of AR-V7 in men with advanced prostate cancer. Ann. Oncol. 26, 1859-1865. (Link)