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IMPaCT Investigator Highlights (Text Version) - Dr. Arul M. Chinnaiyan

Title: Therapeutic Targeting of SPINK-1-Positive Prostate Cancer

Investigator: Arul M. Chinnaiyan, MD, PhD; University of Michigan Medical School

My current grant is focused on therapeutic targeting of this molecule called SPINK-1. We discovered that about 10% of prostate cancer patients have elevated SPINK-1 levels which we find in more aggressive prostate cancers, and this is in a population of patients that don’t have these molecular aberrations called gene fusions. And what’s intriguing is—is that they’re actually blocking monoclonal antibodies that we can take advantage of to block this molecule called SPINK-1 and so we’re evaluating that as a potential therapy for prostate cancer patients that are positive for this marker called SPINK-1.

I think the hope is—is that the impact might parallel what’s happened in breast cancer where about 20% of patients have over-expression of this gene called erb2 and that can be targeted with this monoclonal antibody called Herceptin. So we believe that we’ve identified somewhat of an equivalent for prostate cancer so the thought is that we’ll be able to use antibodies against SPINK-1 to block that cancer-causing gene. Another interesting observation we have is that SPINK-1 functions through this receptor called EGFR or EGF receptor and there are already FDA-approved drugs against that receptor that we believe might be useful in patients that have elevated SPINK-1. So we’re evaluating that as well.

So our accomplishments so far really from a Department of Defense funding was really identifying that 10% of patients have this over-expression of SPINK-1, and their disease is more aggressive than those that don’t. And we’ve gone on to do the preclinical steps of evaluating a therapy against SPINK-1 in both in vitro models as well as in mouse—mouse models in vivo. So the thought is that we—the next steps really are to see if we can translate this clinically to see if antibodies against SPINK-1 or antibodies against EGF receptor can work in patients that have a SPINK-1 positive prostate cancer. So that’s, I think, our ultimate goal.

Collaborative research I think is key to really advance findings to actual clinical use. It’s very difficult to really translate these findings in an isolated laboratory, and you need to work with different individuals at often times different institutions with different disciplines to actually make that happen.

We collaborate considerably at the University of Michigan. We have teams of individuals and faculty focused on bioinformatics, medical oncology, pathology, urology, and so forth but we also collaborate in different—with other investigators at different institutions. For example, one of our long-term collaborators has been Mark Rubin who is a prostate pathologist at Cornell University.

The PCRP I think is critical—is a critical engine to drive prostate cancer research. I would say that the discoveries that I’ve described today would not have been made without funding from the Department of Defense. It’s difficult to really carry out some of this groundbreaking research without support and funding from agencies like the Department of Defense which has been really funding higher-risk research that potentially other agencies like the National Cancer Institute may not fund.

The PCRP has impacted my career from early on at the stages of when I first began working on prostate cancer and have consistently funded my lab probably for the last decade, but even more importantly they’ve been funding a number of trainees in my laboratory as well as junior faculty who have received New Investigator Awards and have gone onto faculty positions at other institutions and I think they’ve established their careers as well. So I think they’ve had an impact merely beyond—merely beyond just my laboratory but also on the various trainees that have—that I’ve mentored over the past.

It’s a great program that funds innovative ideas, high-risk research and I think it’s—it’s a great program to—especially early on in your career establishing yourself either as a—a Graduate Student or as a Postdoctoral Fellow and as a new investigator I think it’s—it’s a great resource to establish a laboratory.