Scientist reveals the impact of mitochondria in metastatic prostate cancer

Prostate cancer that has spread to other regions of the body is commonly treated with hormone treatment, but many individuals develop resistance to it, making their disease more aggressive and potentially fatal.

Scientist reveals the impact of mitochondria in metastatic prostate cancer

Image Credit: University of Colorado Anschutz Medical Campus.

One of the big challenges we have in the field is that the majority of prostate cancer therapies target hormone —the androgen axis. But nearly all patients develop resistance to those drugs and then get a more aggressive disease that starts moving to other parts of the body. It’s been confined to the prostate, but now it might move over to the bones or the liver, or the lungs. That’s really a big problem, because when you start to compromise the vital organs, the patient eventually will die.”

Cecilia Caino, PhD, Researcher, Department of Pharmacology, School of Medicine, University of Colorado Anschutz Medical Campus

Caino was mentored by the University of Colorado Cancer Center.

Caino received an Idea Award from the Peer-Reviewed Cancer Research Program of the United States Department of Defense in spring 2021 to explore the role of mitochondria—microscopic energy factories in cells that help break down food into fuel—in metastatic prostate cancer.

Caino and the co-investigators revealed that tumor cells employ mitochondria to control their development and sense stress, which can kill a tumor cell if it is not managed, in a preliminary study just published in the journal Molecular Cancer Research. The research is supported by the American Cancer Society, the Boettcher Foundation, and the National Institute of General Medical Sciences, in addition to the Department of Defense.

We know that tumor cells are very resistant to stress in general; that’s what makes them so hard to target with therapies. But when the tumors grow too fast, they start running out of nutrients to keep building. They utilize this mitochondrial pathway that we describe to slow down for a moment, adapt, and expand their capacity to synthesize more blocks to build the cells.”

Cecilia Caino, PhD, Researcher, Department of Pharmacology, School of Medicine, University of Colorado Anschutz Medical Campus

A compound to target

In metastatic prostate cancer tumors, Caino and research colleagues discovered that a mitochondrial protein called MIRO2 is overexpressed.

Caino hypothesizes that targeting MIRO2 can prevent the mitochondrial process that inhibits tumor cells from destroying themselves by expanding too quickly, based on previous findings that MIRO2 collaborates with two other proteins known as GCN1 and GCN2 to help metastatic prostate cancer cells tolerate conditions where normal cell growth is inhibited.

Our next step is to treat animal models that have metastases and see if we can eliminate the tumor or prevent the metastasis from even occurring in the first place. We are also learning a lot more about the complex, because we want to know how it is regulated. That will help us stratify patients who will benefit from the therapy from those who will not.

Cecilia Caino, PhD, Researcher, Department of Pharmacology, School of Medicine, University of Colorado Anschutz Medical Campus

The researchers will first treat the metastasis using an existing drug that is used to treat acute lymphocytic leukemia, but Caino intends to develop a treatment that will prevent the complex from developing in the first place.

Caino also added, “A lot of times drugs work for a while, then they stop working. You already have to be thinking about what you’re going to do when that drug doesn't work anymore. Hopefully we can come up with a strategy to stop the process farther upstream.”

Milestone research

Caino is extremely excited about this study because it is Caino’s first peer-reviewed publication as a senior corresponding author. It is also been 22 years since Caino first worked in a lab.

I decided to start a new line of research that did not stem directly from my postdoctoral studies. I also chose to begin my lab with a couple of graduate students and a technician, investing in their training while remaining involved in bench work myself. Walking this long, winding road was challenging and called upon every single skill and strength I had,” Caino concluded.

Source:
Journal reference:

Furnish, M., et al. (2022) MIRO2 Regulates Prostate Cancer Cell Growth via GCN1-Dependent Stress Signaling. Molecular Cancer Research. doi.org/10.1158/1541-7786.MCR-21-0374.

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