New approach to treat advanced prostate cancer

Researchers from the University of Liverpool and the Sichuan Antibiotics Industrial Institute have discovered a novel treatment for advanced prostate cancer which raises concerns about the way treatment is currently conducted (University of Liverpool, 2017).

Professor Youqiang Ke, from the University of Liverpool’s Institute of Translational Medicine, led the research, published in Oncotarget, which focused on studying the molecular mechanisms involved in the progression of prostate cancer cells.

Prostate cancer is the most common male cancer and over 47,000 men are diagnosed with it in the UK every year. About 12,000 men die from prostate cancer each year in the UK and one in eight men will get it in their lifetime.

Since the growth of prostate cells rely on androgens, prostate cancer treatment has relied on androgen-deprivation therapy (ADT) for over four decades. ADT is effective initially and the cancer disappears quickly. But in almost all cases, the cancer will come back after about two years and this re-appeared cancer does not rely on androgen for its growth anymore and is thus called androgen-independent cancer or castration-resistant cancer (CRPC). ADT is not effective to CRPC and CRPC is currently incurable.

The key question is how the prostate cancer cells are converted from androgen-dependent to androgen-independent state. The most common theory is that the androgen receptor (AR) has amplified its sensitivity in CRPC cells and it can make use of a very little amount of remaining androgen (after ADT) to continue supporting the cancer cells to grow and to expand. Based on this theory, the treatment of CRPC should be further ADT to block the last drop of androgen. Currently, this approach does not work effectively.

Youqiang Ke said “My research team has focused our effort on studying the molecular mechanisms involved in malignant progression of prostate cancer cells and identified several important cancer-related genes which were not previously implicated in any cancerous diseases. One of the cancer-promoting gene is called FABP5 which exhibited the highest potential to be a treatment target. During the past two decades, we have systematically studied its biological function and discovered its crucial role in the malignant progression of CRPC. During the investigation on the molecular mechanisms on how FABP5 facilitates cancer development and spread, we found a novel FABP5-related signalling pathway in CRPC.”

The study suggests that it is this FABP5-related pathway, not the androgen or AR-related pathway that is a more important route for cancer cells to transduce their malignant signals. Also, the FABP5-related pathway has gradually replaced the AR-related pathway as the reduced androgen-dependency of the CRPC cells. This highlights the fact that ADT treatment will push all cancer cells to the androgen-independent state and eventually do more harm than good.

Youqiang Ke said “This work will raise serious questions on the current way for CRPC treatment which has been followed for the past 4 decades. It provided a realistic hope for a new drug to target FABP5 to effectively treat CRPC, thus it may mark a significant progress in CRPC research and may be a turning point on CRPC treatment.”

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