We have recently developed the first genetic mouse model for therapy and analysis of metastatic prostate cancer. Now we can test if and how modern concepts of cancer evolution can outperform the 80-year-old standard of care - hormone deprivation therapy - and turn lethal prostate cancer into a curable disease.
Lloyd Trotman’s recent research path begins at his discovery some years ago that the loss of a single copy of a master tumor suppressing gene called PTEN is sufficient to permit tumors to develop in animal models of prostate cancer. His team later found that complete loss of PTEN paradoxically triggers senescence, an arrested state that delays or blocks cancer development in affected cells. These findings explained why many patients only display partial loss of this tumor suppressor when diagnosed with prostate cancer. Now the team is researching ways to restore the PTEN protein levels in these patients. This therapeutic approach could slow disease progression and thus greatly reduce the need for surgical removal of the prostate or similar drastic interventions that carry the risks of incontinence and impotence. Their second approach to combat prostate cancer is to model the lethal metastatic disease in genetically engineered mice. They are developing a novel approach that allows for quick generation and visualization of metastatic disease. The efficacy of existing and novel late-stage therapies, such as antihormonal therapy, can then be tested and optimized in these animals. At the same time, the Trotman lab is exploring the genome alterations associated with metastatic disease and with resistance to therapy. To this end, they use single- and multicell genome sequencing techniques developed at CSHL by Drs. Wigler and Hicks.
Cho, H. and Herzka, T. and Zheng, W. and Qi, J. and Wilkinson, J. E. and Bradner, J. E. and Robinson, B. D. and Castillo-Martin, M. and Cordon-Cardo, C. and Trotman, L. C. (2014) RapidCaP, a novel GEM model for analysis and therapy of metastatic prostate cancer, reveals Myc as a driver of Pten-mutant metastasis. Cancer Discovery, 4(3) pp. 318-33.
Labbé, D. P. and Nowak, D. G. and Deblois, G. and Lessard, L. and Giguère, V. and Trotman, L. C. and Tremblay, M. L. (2014) Prostate cancer genetic-susceptibility locus on chromosome 20q13 is amplified and coupled to androgen receptor-regulation in metastatic tumors. Molecular Cancer Research, 12(2) pp. 184-189.
Naguib, A. and Trotman, L. C. (2013) PTEN plasticity: how the taming of a lethal gene can go too far. Trends In Cell Biology, 23(8) pp. 374-379.Additional materials of the author at
CSHL Institutional Repository