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.
One experiment: Observing cancer’s progress in a mouse prostate
March 14, 2019
Experts have long known that tumors arise from the migration of cancer cells across organs. But observing the progression of those cancer cells in high resolution, and in turn being able to more effectively hinder their advances, has been a challenge for scientists. Now, a cutting-edge technique originally developed by Associate Professor Pavel Osten’s lab...
Study reveals a way to make prostate cancer cells run out of energy and die
April 3, 2018
Cold Spring Harbor, NY — Scientists at Cold Spring Harbor Laboratory (CSHL) have discovered that cells lacking the tumor-suppressor protein PTEN—a feature of many cancers—are particularly vulnerable to drugs that impair their energy-producing mitochondria. Such drugs induce them to literally eat themselves to death, the research shows. Unlike normal cells, cells without PTEN seem driven...
Researchers identify “Achilles’ heel” of PTEN that helps drive prostate cancer progression
February 13, 2017
New research from the Trotman lab has revealed that, in prostate cancer, a protein known as Importin-11 is the ‘Achilles’ heel’ that is required for the stability of the PTEN tumor suppressor. In fact, loss of Importin-11 predicted relapse and metastasis in patients who had had their prostate removed.
No (real) moustache required to join the “Movember” party
November 15, 2016
LabDish blog Prostate cancer is the most common non-skin cancer among American men, but most of the prostate cancer researchers at CSHL have zero risk of developing the disease. The majority of the prostate cancer researchers at CSHL are part of the population that will never get this disease: women. Growing a mo’ for “Movember”—a...
Movember: Fighting for health in the Lab and the gym
November 20, 2015
LabDish blog Even considering that he’s faced pro fighters while training in jiu-jitsu, prostate cancer is by far Dawid Nowak’s most formidable opponent. In the lab of Lloyd Trotman, he’s using an incredibly powerful new genetic engineering tool and an extremely sensitive sequencing technique to take prostate cancer down. In a fight, strategy sometimes proves stronger...
Third-year student Abram Handly Santana explores the pancreatic tumor microenvironment
August 1, 2015
Most people don’t think about their pancreas very often. Buried deep inside the abdomen, wedged between the stomach and the spine, we can’t even feel it. But there it is, day in and day out, working away to make the enzymes that digest our food and the hormones that control our blood sugar. Having a...
An immune system marker for therapy-resistant prostate cancer
June 4, 2015
Interleukin-6 signaling plays role in switching mouse prostate cancer to more aggressive, therapy-resistant form Cold Spring Harbor, NY — You are a patient who has just been treated for a serious illness but neither you nor your doctor knows how likely it is that you—in comparison with other patients—will actually be helped by the treatment....
Pershing Square Foundation establishes $10 million endowment to support CSHL life science research
June 1, 2015
Cold Spring Harbor, NY — Cold Spring Harbor Laboratory (CSHL) announced today that The Pershing Square Foundation (PSF) has awarded the institution $10 million to support its leading biology and genetics research and education programs. The uniquely structured grant reflects a commitment by The Pershing Square Foundation to support exceptional leadership and innovative organizations that...
Study revises standard theory of how PTEN, a critical tumor suppressor, shuts off growth signals
April 9, 2015
The Trotman lab, in collaboration with the Pappin and Joshua-Tor labs, has found that the tumor suppressor PTEN uses microtubules to travel around the cell. The work challenges previous models for how the protein moves and provides new understanding that may be useful for targeted drug development.
One experiment: Cellular highways carry anti-cancer cargoes
April 9, 2015
Super-resolution microscopy provides the surprising answer We’re swimming deep inside the cytoplasm, the watery interior of a cell, which, at the scale of this image, is living room-sized. The membrane—the oily wall that protects everything inside—is perhaps 20 feet away. The green “threads” crisscrossing around us are microtubules, gossamer-thin cargo roads that project inward from...
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 atCSHL Institutional Repository