Cold Spring Harbor Laboratory
It is until now a tremendous challenge to analyze the genetic evolution of lethal prostate cancer in patients. Our newly developed RapidCaP mouse system for metastatic prostate cancer allows us to analyze genomes of single cancer cells.
With this technology, we study the evolution of cancer genomes as cells metastasize throughout the body or resist therapy. Our ultimate goal is to establish the RapidCaP system as the leading platform for prostate cancer drug discovery.
Single Cell Analysis of Prostate Cancer Evolution To Metastasis & Therapy Resistance
Castration resistance kills some 250,000 US prostate cancer (PC) patients every year. Human PC is characterized by large variability in disease outcomes. We hypothesize that spontaneous gene changes are behind much, if not most of this variability. Yet, there is a lack of knowledge on such features that predict the different outcomes better than microscopic disease analysis.
“Winning the prize means]the freedom to tackle the most exciting question that I can think of.”
Our newly developed RapidCaP mouse system for metastatic prostate cancer analysis and therapy recreates this variability. We see variable latency to metastasis and castration response/ relapse patterns. We hypothesize that also in mouse, the accumulation of spontaneous genetic changes is behind most of this variability. A team of researchers at CSHL has now developed genome sequencing based technique to infer the evolutionary relationships between cells that come from a cancer and disseminate throughout the body. However, it has remained logistically too challenging to apply this advance to patients. Here we propose to use our RapidCaP system to develop the needed expertise for understanding the principles of disease spread and hormone therapy resistance, so that in the future, we can apply our know-how to understanding metastatic disease progression and therapy resistance in human.
“I think true innovation is judged by popularity, it needs to have an impact on many people. If a breakthrough fails to break into society, then it fails to move us forward. In respect to my research, this means that if we successfully evolve the RapidCaP system to be widely accepted and the best platform for pre-clinical drug screening and prostate cancer genome evolution, then I would consider it truly innovative.”