Recurrent fusion genes found in 60 to 70 per cent of prostate cancers: Dr Arul Chinnaiyan

Interview/ Dr Arul Chinnaiyan

Dr Arul Chinnaiyan Dr Arul Chinnaiyan

Dr Arul Chinnaiyan was awarded this year’s Sjoberg Prize in cancer research for establishing that the fusion gene is responsible for more than half the prostate cancer cases in the world. In an exclusive interview, Chinnaiyan talks about fusion gene and how it is going to help in treating prostate cancer. Excerpts:

What is fusion gene?

A fusion gene occurs when two genes, which normally reside in different parts of the genome, come together and get fused. The fusion of genes can initiate the development of cancers in which they are found.

Why is it important in prostate cancer?

It is important in prostate cancer because recurrent fusion genes are found in upwards of 60 to 70 per cent of prostate cancers. The most common gene fusion we discovered is called TMPRSS2:ERG, which is found in about 50 per cent of patients. These prostate cancer gene fusions are typically regulated by male hormones and cause increased levels of cancer driver genes. When recurrent gene fusions are discovered for a particular cancer type they are considered the molecular cause of the cancer. In addition, to serving as a therapeutic target in prostate cancer, these gene fusions are exquisitely specific for prostate cancer and thus can be used as diagnostic biomarkers.

How is it going to help with diagnosis and treatment?

The TMPRSS2: ERG gene fusion that we identified is an exquisitely specific biomarker of prostate cancer that can be detected in prostate needle biopsies and non-invasively in the urine of men with prostate cancer. In terms of treatment, the gene fusions in prostate cancer are under the control of male hormones, and blocking male hormones is already an established treatment for prostate cancer. Investigations are underway to target the gene fusion product directly or indirectly using a variety of approaches.

Is it relevant in other cancers?

Before the discovery of recurrent gene fusions in prostate cancer, it was thought that gene fusions and translocations were major drivers of liquid cancers and rare soft tissue tumours, but we had found these gene fusions in high prevalence in a common solid tumour, that being prostate cancer. After our discovery, a number of recurrent gene fusions were identified in subsets of other common solid tumours including lung cancer, breast cancer, and melanoma, among others. Perhaps, the most famous being the EML4-ALK gene fusion in lung cancer which can be directly targeted with drugs.

What is your current focus of research?

My research, in general, is focused on precision oncology with a heavy focus around prostate cancer. Since I was awarded this prize for the discovery of recurrent gene fusions in prostate cancer, I plan to use the funds from this award to fuel our efforts in therapeutically targeting the products of these gene fusions—which are oncogenic transcription factors. We will develop direct and indirect approaches to target oncogenic transcription factor in cancer.

Dr Arul Chinnaiyan is director of the Michigan Centre for Translational Pathology and SP Hicks endowed professor of pathology and urology at the University of Michigan