Loss of ZFP36 as a Biomarker of Lethal Prostate Cancer

Project Overview

• Zinc finger protein 36 (ZFP36) is an RNA-binding protein associated with the rapid progression of prostate cancer as well as other low-grade diseases.
• ZFP36 expression may additionally serve as a predictive biomarker for patients that may respond to nuclear factor kappa B (NFκB) inhibition. This type of biomarker allows much earlier patient stratification than relying on clinical surveillance or watchful waiting.
• Dana-Farber scientists have created a prostate cancer detection method based on the expression of ZFP3 that is available for licensing.

Technology

The invention provides methods for screening and diagnosing prostate cancer based on a correlation between cancer cell growth, cancer lethality or recurrence and the expression level of ZFP36, or NEDD9 and PTEN in conjunction with ZFP36. 

NFkB is a central regulator of cell survival and proliferation and thus plays an important role in cancer growth and development. NFkB signalling pathway regulates gene transcription in response to growth factors. ZFP36 encodes for tristetraprolin (TTP) which facilitates the decay of mRNAs of some genes induced by NFkB. By this means, ZFP36 negatively modulates pro-inflammatory factors which can lead to the rapid development of cancer cells. 

Data shows that the loss of ZFP36 alters the cell state that is driven by PTEN loss, a separate tumor suppressor linked to prostate cancer. ZFP36 deletion could exert anti-tumorigenicity actions due to effects on inflammation and metabolism in a diethylnitrosamine (DEN) hepatocarcinogenesis model. But during hepatic tumor progression, ZFP36 acted as tumor-suppressor by inhibiting cell proliferation and migration, and slightly increasing chemosensitivity to doxorubicin and sorafenib. 

Team Members: Christopher Sweeney, MBBS, Curtis Huttenhower

Applications

• ZFP36 can be used to identify patients with aggressive prostate cancer who would benefit from surgery or radiation.
• It can also serve as a diagnostic to determine patient susceptibility to prostate cancer by screening the expression levels of ZFP36, or NEDD9 and PTEN in conjunction with ZFP36.
• The present invention also claims methods for treating prostate cancer comprising a treatment or monitoring based on the expression level of ZFP36, or NEDD9 and PTEN in conjunction with ZFP36. 

Opportunities

Dana-Farber is seeking partners to license this technology.