黑料吃瓜资源

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. This is often the situation with prostate cancer, one of the deadliest and most highly prevalent cancers. While hormone therapy can help, patient responses vary widely, and it鈥檚 still unclear why some types of prostate cancer seem to be resistant to the therapy.

In work published today in Cancer Discovery, a team led by Associate Professor Lloyd Trotman at 黑料吃瓜资源 (CSHL) shows how signaling by an immune system component called interleukin-6 (IL-6) appears to play an important role in driving particularly aggressive and therapy-resistant prostate cancer.

鈥淥ur research suggests that IL-6 could be a marker for when the disease switches to a more dangerous state that is ultimately hormone therapy-resistant,鈥� says Trotman.

The results could have important implications for human prostate cancer. 鈥淭he gain could be immense, because today’s problem is that the variability in response of humans to hormone therapy is amazing,鈥� Trotman says. 鈥淔or one man this therapy might be great, might reduce disease burden dramatically for many, many, years, and be an extreme benefit,鈥� he says. 鈥淔or others there’s almost no response, and it’s still not clear to clinicians who is who.鈥�

Being able to predict which patients would benefit from hormone therapy 鈥渨ould be amazing,鈥� Trotman says. 鈥淲e are really hopeful that translating the IL-6 discovery into the clinics could help us stratify patients into good responders and bad responders. For any hospital this would be a major breakthrough.鈥�

Trotman and his team, which included Dawid Nowak, Ph.D., a postdoctoral investigator who is the paper’s first author, looked for cellular signals that led to metastasis and hormone therapy resistance in a genetically engineered mouse model for metastatic prostate cancer. They found that the combined loss of two genes, PTEN and p53—closely associated with prostate cancer metastasis—led to the secretion of IL-6. Signaling by IL-6 was then responsible for activating a powerful cancer gene called MYC, which drives cell proliferation and disease progression.

鈥淚t suggested immediately that cell-cell communication is very, very important to make the cells resistant to therapy and very aggressive,鈥� says Trotman.

The involvement of the MYC pathway suggests that it could potentially serve as a target of drugs against prostate cancer, Trotman says. The team鈥檚 next step is to study IL-6 signaling in humans. 鈥淚L-6 detection in blood has been developed to a high art,鈥� Trotman says. 鈥淭here are very good tools, which have been tested in the hospital setting.鈥�

Written by: Sandeep Ravindran, Science Writer | [email protected] | 516-367-8455

Funding

The work described in this release was supported by the Pershing Square Sohn Cancer Research Alliance; the American Cancer Society; the National Institutes of Health (CA137050); the Department of Defense (W81XWH-14-1-0247), the STARR Foundation (I8-A8-112), the Robertson Research Fund of CSHL; and the CSHL Cancer Center (through NIH Support Grant 5P30CA045508).

Citation

鈥淢YC Drives Pten/Trp53-Deficient Proliferation and Metastasis due to IL6 Secretion and AKT Suppression via PHLPP2鈥� appeared online in Cancer Discovery on June 3, 2015. The authors are: Dawid G. Nowak, Hyejin Cho, Tali Herzka, Kaitlin Watrud, Daniel V. DeMarco, Victoria M.Y. Wang, Serif Senturk, Christof Fellmann, David Ding, Tumas Beinortas, David Kleinman, Muhan Chen, Raffaella Sordella, John E. Wilkinson, Mireia Castillo-Martin, Carlos Cordon-Cardo, Brian D. Robinson, and Lloyd C. Trotman. The paper can be obtained online at: