In a new study, researchers have identified the drivers of a crucial gene involved in prostate cancer, revealing new targets for drug design.
They identified a set of cis-regulatory elements – namely enhancers and the promoter – in the non-coding region of the genome, which affect the expression of FOXA1 gene, one of the major drivers or oncogenes involved in prostate cancer development.
The research was conducted by Scientists at Princess Margaret Cancer Centre.
Scientists have begun mining the dark or non-coding portion of the genome – about 98% of the genome – as a potential source of new targets for drug development.
They realize that hidden amongst the non-coding DNA are crucial elements that not only control the activity of thousands of genes but also play a major role in many diseases.
Exploring this area could provide important sequencing clues for potential cures.
FOXA1 has long been recognized as playing an important role in malignancy, but it is one of the most challenging targets for drug development in cancer.
Often termed “undruggable,” it is extremely difficult to inhibit due to its lack of easily accessible “pockets” for small-molecule therapies to slip into to break the deadly uncontrolled cell growth leading to cancer.
Scientists the world over are looking at different ways to target FOXA1 since it is implicated in many cancers including breast, prostate, lung, thyroid and esophageal squamous cell carcinomas.
In the study, the research team examined 200 human prostate tumors and identified six mutated cis-regulatory elements that control FOXA1 expression.
They further demonstrated that removing these elements reduced FOXA1 expression and impaired growth of prostate cancer cells.
This allows them to expand their tool kit of potential therapies against prostate cancer.
Prostate cancer is the second most commonly diagnosed malignancy among men worldwide, with an estimated 1.3 million new cases worldwide in 2018.
Treatments typically fail in 30 percent of patients within 10 years, resulting in cancer spreading to other sites.
Despite the efficacy of anti-androgen therapies for metastatic cancer, recurrence ultimately develops into lethal cancer.
This spurs our need to improve our biological understanding of how prostate cancer develops and to find novel strategies to treat patients.
The lead author of the study is Dr. Mathieu Lupien, a Senior Scientist at Princess Margaret Cancer Centre.
The study is published in Nature Communications.
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