Ph.D., University of Zurich, 2001
|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.
RapidCaP, a novel GEM model for metastatic prostate cancer analysis and therapy, reveals myc as a driver of Pten-mutant metastasis. Cho H, Herzka T, Zheng W, Qi J, Wilkinson JE, Bradner JE, Robinson BD, Castillo-Martin M, Cordon-Cardo C, Trotman LC. Cancer Discov. 2014 Mar;4(3):318-33. doi: 10.1158/2159-8290.CD-13-0346. Epub 2014 Jan 20.
PMID: 24444712 [PubMed - in process] Related citations Select item 24392697
Turning off AKT: PHLPP as a drug target. Newton AC, Trotman LC. Annu Rev Pharmacol Toxicol. 2014;54:537-58. doi: 10.1146/annurev-pharmtox-011112-140338. PMID: 24392697 [PubMed - in process] Related citations Select item 24379448
Prostate cancer genetic-susceptibility locus on chromosome 20q13 is amplified and coupled to androgen receptor-regulation in metastatic tumors. Labbé DP, Nowak DG, Deblois G, Lessard L, Giguère V, Trotman LC, Tremblay ML. Mol Cancer Res. 2014 Feb;12(2):184-9. doi: 10.1158/1541-7786.MCR-13-0477. Epub 2013 Dec 30. PMID: 24379448 [PubMed - in process] Related citations Select item 23578748
PTEN plasticity: how the taming of a lethal gene can go too far. Naguib A, Trotman LC. Trends Cell Biol. 2013 Aug;23(8):374-9. doi: 10.1016/j.tcb.2013.03.003. Epub 2013 Apr 9. Review.
PMID: 23578748 [PubMed - indexed for MEDLINE] Related citations
Scientists develop powerful new animal model for metastatic prostate cancer
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Lloyd Trotman receives Pershing Square Sohn Prize for cancer research
May 5, 2014