Abstract
Castration resistant-prostate cancer is largely impervious to feather hormonal therapy and hence the outlook for patients is grim. Here we use an approach to attach the recently discovered Achilles heel. The experimental treatment established in this study is based on the recent discovery that it is the FABP5-PPARγ-VEGF signalling axis, rather than the androgen receptor pathway, played a dominant role in promoting the malignant progression of castration resistant prostate cancer cells. Treatments have been established in mice by suppressing the biological activity of FABP5 using a chemical inhibitor SBFI26. The inhibitor significantly suppressed the proliferation, migration, invasiveness and colony formation of PC3-M cells in vitro. It also produced a highly significant suppression of both the metastases and the primary tumours developed from cancer cells implanted orthotopically into the prostate glands of the mice. The inhibitor SBFI26 interferes with the FABP5-PPARγ- signalling pathway at the initial stage of the signal transduction by binding competitively to FABP5 to inhibit cellular fatty acid uptake. This avoids the fatty-acid stimulation of PPARγ and prevents it activating the down-stream regulated cancer-promoting genes. This entirely novel experimental approach to treating castration- resistant prostate cancer is completely different from current treatments that are based on androgen-blockade therapy.
Highlights
Prostate cancer is an important cause of mortality in men, mainly in countries where a high dietary ratio of fatty acids is consumed [1]
Since it was discovered that prostate cancer cell growth is dependent on the promoting effect of male hormone supplied through peripheral blood circulation [23], Androgen deprivation therapy (ADT) targeting androgen receptor (AR) and circulating androgen has been the main therapeutic method to treat prostate cancer patients during the past 4 decades
The conversion of androgen-dependent cancer cells to androgen independent castrationresistant prostate cancer (CRPC) cells is a fundamental change and the molecular mechanisms involved in this change is not fully known
Summary
Prostate cancer is an important cause of mortality in men, mainly in countries where a high dietary ratio of fatty acids is consumed [1]. Androgen deprivation therapy (ADT) is the first line treatment for advanced prostate cancer and it is initially effective. In most cases the disease eventually relapses within 2–3 years, with a lethal castrationresistant prostate cancer (CRPC); this cannot be effectively treated with ADT anymore [2]. Fatty acids are active components of many biological processes, and are essential signal molecules in pathways involved in prostate cancer progression, and can increase the risk of advanced prostate cancer [6, 7] and play an important role in carcinogenesis and metastasis of cancer cells [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
