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New approach to treating advanced prostate cancer discovered

Cancer cells

Researchers from the University and the Sichuan Antibiotics Industrial Institute in China have discovered a novel treatment for advanced prostate cancer which raises concerns on the way treatment is conducted presently.

Professor Youqiang Ke, from the University’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.

130-a-day

Prostate cancer is the most common male cancer and over 47,000 men are diagnosed with prostate cancer in the UK every year-that’s 130 men every day.

About 12,000 men die from prostate cancer each year in the UK and one in eight men will get prostate cancer in their lifetime.

Since the growth of prostate cells rely on male hormone (Androgen), prostate cancer treatment has always been rely on Androgen-Deprivation Therapy (ADT) for more than four decades.

ADT is effective initially and the cancer disappeared 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 thus called androgen-independent cancer or castration-resistant cancer (CRPC).

ADT is not effective to CRPC and CRPC is currently incurable.

Theory

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.

Crucial role

Professor 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.”

‘More harm than good’

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.

Professor Ke adds: “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.”

The full study, entitled ‘Inhibitor SBFI26 suppresses the malignant progression of castration-resistant PC3-M cells by competitively binding to oncogenic FABP5’, can be found here.

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