Jenny Freedman, PhD, member of the Duke Cancer Institute Center for Prostate and Urologic Cancers, explains how a natural gene-splicing process can run amuck, producing prostate cancer cells. Freedman’s team’s discovery, published in npj Precision Oncology, provides a promising new target for cancer treatment.
Your team has discovered something new about the way prostate cancer cells grow and divide. Can you tell us what you learned?
During normal growth and development, cells in our body use a limited number of genes to make a large number of proteins, which in turn enable cells to perform their functions. Usually, this protein making activity occurs through an orderly process called splicing. But if this splicing process goes haywire, then our cells produce abnormal proteins, which can result in diseases, including prostate cancer.
We also noticed something else very important. Abnormal splicing in cells appears to be associated with two things: how aggressively the prostate cancer cells behaved, and how quickly the cancer recurred after treatment. And this atypical splicing was different in cancer cells from White men and from Black men.
How could your discovery improve the outlook for people living with advanced prostate cancer?
We’re especially hopeful that our discovery will lead to new ways to treat prostate cancer. Not only new therapies—new ways for predicting who will respond to those therapies and how long their responses will last.
How will this new information help your team take the next steps in finding a cure?
We’re going to study more precisely how these abnormally spliced genes affect the growth and spread of prostate cancer in the research laboratory, using cells and mouse models. We believe that our work is preparing the way for a new class of drugs that will target the splicing process that produces cancerous proteins. In other words, our work has the potential to change the paradigm for precision oncology for prostate cancer. We couldn’t be more motivated to pursue these promising targets.
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The patients who participated in this study to bring these results to light and our colleagues who passionately championed this study.
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The BioRepository & Precision Pathology Center, a shared resource of the Duke University School of Medicine and DCI, for collecting the biospecimens used under Institutional Review Board oversight of this work.
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The assistance of the Duke Molecular Physiology Institute Molecular Genomics Core for generating the genotyping data, which enabled estimation of patient genetic ancestry.
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The assistance of the Sequencing and Genomics Technologies Shared Resource of the Duke University School of Medicine and DCI for generating the sequencing data, which enabled discovery of differences in splicing.
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The work was supported by a Department of Defense Prostate Cancer Research Program Health Disparity Research Award, National Institutes of Health Basic Research in Cancer Health Disparities R01 Award, and a Movember Foundation – Prostate Cancer Foundation VAlor Challenge Award.
