PhD candidate and medical student Tanner Zachem and urologic oncologist Michael Abern, MD. Photo by Eamon Queeney.
An Innovator Sparks Innovation
Published
Walt and Arlene Simmons didn’t just hope for better treatment. They funded it.
Prostate Tumor ID, developed by urologic oncologist Michael Abern (left) and biomedical engineering PhD candidate and medical student Tanner Zachem, promises to help surgeons precisely “see” cancerous prostate tissue in real time. Photo by Eamon Queeney.
Walt Simmons is a seasoned mechanical engineer with an entire wall in his West Virginia home decorated with his patents. Still professionally active in his seventies, he owns and operates a hydro-electric facility that he purchased in a dilapidated condition.
“Even though I knew nothing about dams at the time,” Walt said.
“And even though it was junky, and filthy,” said Arlene.
“So I thought, well, this is a challenge,” said Walt, a playful gleam in his eye.
Walt’s love of a good challenge, and Arlene’s lifelong devotion to supporting her husband’s engineering ventures, soon drew the couple to ask Walt’s oncologist at Duke Cancer Institute, Daniel George, MD, a question. What could they do to advance treatments for the prostate cancer that nearly cost Walt his life?
“When Dr. Dan George pointed out that Duke was uniquely positioned to bring engineers and oncologists together to solve real problems, we knew we wanted to be part of it. I’ve always been fascinated by the process of discovery,” said Walt.
George, co-chair of the DCI’s Center for Prostate and Urologic Cancers, suggested an organic approach to fostering new collaborations: a monthly meeting between prostate cancer clinical researchers and biomedical engineers from Duke’s Pratt School of Engineering to identify and solve prostate cancer challenges. “Bringing biomedical engineers from Pratt to the table is special. That would not have happened without a funding incentive,” George said.
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We wanted to do something that would matter. Not just for Walt, but for other families facing prostate cancer. Supporting this kind of research felt like the right way to give back.
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Arlene Simmons
A Device is Born
A prototype of Prostate Tumor ID. Photo by Eamon Queeney.
The Simmons decided to fund seven “stimulus” awards, each worth $100,000, to kick start collaborative research. One of the first awards sparked the development of a device called Prostate Tumor ID that its inventors hope will improve outcomes for men with prostate cancer who have surgery to remove the prostate.
“Prostate cancer is notoriously hard to visualize during surgery,” said Michael Abern, MD, associate professor of urology at Duke. “Even with laparoscopic cameras, it’s difficult to distinguish cancerous tissue from healthy tissue in real time.”
A surgeon’s ability to successfully make that distinction profoundly impacts a patient’s outcome. If they cut away too little tissue, some cancer could remain. If they take too much, urinary and sexual function could suffer.
Urologists’ dream scenario, said Abern, would be a device designed to enhance a surgeons’ ability to precisely “see” the cancerous prostate tissue in real time — while they are performing a surgery.
Abern and Patrick Codd, MD, associate professor of neurosurgery, proposed to reengineer a tool already in use by Duke neurosurgeons to operate on brain tumors, making it suitable for prostatectomies.
The team assigned Tanner Zachem, a PhD candidate in biomedical engineering, to make a prototype of “Prostate Tumor ID” and test it. Zachem has also begun his first year of medical school at Duke this fall.
Zachem said that the Simmons stimulus grant accelerated the pace of device development
A prototype of Prostate Tumor ID. Photo by Eamon Queeney.
“Within one month of hearing about the stimulus grant, our team presented a prototype to Mr. and Mrs. Simmons. And just weeks later, boxes containing mechanical parts started arriving. And now, we’re generating a significant amount of data,” said Zachem. “I’m so grateful to the Simmons for jumpstarting my career.”
The resulting new tool is a compact, high-tech device that fits inside a 15mm laparoscopic port. It uses advanced imaging and tissue identification technology to instantly detect cancerous cells during surgery, giving surgeons immediate feedback on where to cut — and where to stop.
This past summer, Zachem and Duke’s urologists began testing TumorID. “This pilot funding will allow us to ultimately pursue additional funding to extend this imaging technology to a form that can be used during minimally invasive surgery,” Abern said.
For Walt and Arlene, the journey has been deeply personal — but also profoundly hopeful.
Arlene Simmons summed up the couples’ motivation for funding the stimulus awards. “We wanted to do something that would matter. Not just for Walt, but for other families facing prostate cancer. Supporting this kind of research felt like the right way to give back.”
A new study led by Duke Cancer Institute (DCI) researchers offers important insights into that challenge in advanced prostate cancer and could help pave the way for more personalized treatment approaches in the future.The research, published recently in Cancer and led by Jennifer Freedman, translational scientist with the DCI Center for Prostate and Urologic Cancers, focused on molecules known as ceramides and how they may influence treatment outcomes in patients with metastatic castration-resistant prostate cancer, an advanced form of the disease that continues to grow despite hormone-suppressing therapies.The study grew out of two innovative Duke-led clinical trials, Abi Race and PANTHER, which enrolled approximately an equal numbers of Black and white patients with advanced prostate cancer. This approach allowed researchers to study treatment outcomes while also examining biological factors that may influence response to therapy.Studies show Black men are disproportionately affected by prostate cancer, experiencing higher rates of diagnosis, metastatic disease, and death from the disease than other populations. Understanding the factors that contribute to those disparities remains a major research priority."We're interested not only in understanding who responds to treatment and who doesn't, but also why," Freedman said. "By building science into clinical trials, we can begin to uncover the biology behind those differences."Patients enrolled in the studies received androgen receptor pathway inhibitors, a class of therapies that block the effects of hormones such as testosterone that help drive prostate cancer growth. Researchers collected blood samples before treatment and during treatment, allowing them to investigate biological changes associated with therapy response.In both clinical trials, investigators observed differences in therapy response among Black and white patients. Despite facing a disproportionate burden of prostate cancer overall, Black patients in the first study shifted toward delays in disease progression. And, in the second study, Black patients showed improvements in radiographic progression-free and overall survival.Previous analysis of samples from the first trial identified genetic variations linked to treatment response. A number of those variations were found in genes involved in ceramide metabolism, leading the team to investigate the ceramides themselves.Ceramides are lipid molecules that play important roles throughout the body. They are involved in cell growth, cell signaling, cell death, and other essential biological processes. Disruptions in ceramide metabolism have also been linked to the development and progression of cancer.When the team analyzed blood samples collected before treatment in both studies, they discovered differences in ceramide profiles between Black and white patients. Black patients had lower overall ceramide levels but higher levels of specific long-chain ceramides, which previous research has associated with worse cancer behavior.As Black patients received androgen receptor pathway inhibitor therapy, levels of potentially harmful long-chain ceramides decreased while levels of shorter-chain ceramides increased. White patients showed the opposite trend, with increases in long-chain ceramides and decreases in shorter-chain versions.Researchers also identified specific ceramide species that were associated with important clinical outcomes, including disease progression, radiographic progression-free survival, and overall survival. Notably, the ceramides linked to outcomes differed between Black and white patients.Together, these findings suggest that ceramide metabolism may contribute to how patients respond to hormone-based therapies.One of the most exciting potential implications of the research is the possibility that ceramides could serve as biomarkers—biological indicators that help predict how a patient is likely to respond to treatment.If validated in additional and larger patient populations, ceramide profiles could help physicians identify which patients are most likely to benefit from androgen receptor pathway inhibitors and potentially guide treatment decisions earlier during care."We can also start thinking about testing combinations of current hormone therapies with treatments that alter ceramide metabolism in models of prostate cancer in the research laboratory," Freedman said. "That approach could potentially improve outcomes even further."The work represents another example of how laboratory science and clinical research can work together to advance cancer care.Freedman credits the study's success to the close collaboration between translational scientists and clinical investigators, as well as the decision to integrate scientific research directly into the clinical trials.The next steps will include validating the findings in additional and larger patient groups and conducting additional studies to better understand how ceramides influence prostate cancer treatment response. Researchers also plan to explore in the laboratory whether targeting ceramide metabolism could enhance the effectiveness of existing therapies.Ultimately, the goal is to develop more precise treatment approaches and address longstanding disparities in prostate cancer outcomes."This is a great example of why it's important to build science into clinical trials," Freedman said. "Every time we learn more about the biology behind treatment response, we're creating opportunities to develop better tools, better therapies, and better outcomes for patients."
A new study led by Duke Cancer Institute (DCI) researchers offers important insights into that challenge in advanced prostate cancer and could help pave the way for more personalized treatment approaches in the future.The research, published recently in Cancer and led by Jennifer Freedman, translational scientist with the DCI Center for Prostate and Urologic Cancers, focused on molecules known as ceramides and how they may influence treatment outcomes in patients with metastatic castration-resistant prostate cancer, an advanced form of the disease that continues to grow despite hormone-suppressing therapies.The study grew out of two innovative Duke-led clinical trials, Abi Race and PANTHER, which enrolled approximately an equal numbers of Black and white patients with advanced prostate cancer. This approach allowed researchers to study treatment outcomes while also examining biological factors that may influence response to therapy.Studies show Black men are disproportionately affected by prostate cancer, experiencing higher rates of diagnosis, metastatic disease, and death from the disease than other populations. Understanding the factors that contribute to those disparities remains a major research priority."We're interested not only in understanding who responds to treatment and who doesn't, but also why," Freedman said. "By building science into clinical trials, we can begin to uncover the biology behind those differences."Patients enrolled in the studies received androgen receptor pathway inhibitors, a class of therapies that block the effects of hormones such as testosterone that help drive prostate cancer growth. Researchers collected blood samples before treatment and during treatment, allowing them to investigate biological changes associated with therapy response.In both clinical trials, investigators observed differences in therapy response among Black and white patients. Despite facing a disproportionate burden of prostate cancer overall, Black patients in the first study shifted toward delays in disease progression. And, in the second study, Black patients showed improvements in radiographic progression-free and overall survival.Previous analysis of samples from the first trial identified genetic variations linked to treatment response. A number of those variations were found in genes involved in ceramide metabolism, leading the team to investigate the ceramides themselves.Ceramides are lipid molecules that play important roles throughout the body. They are involved in cell growth, cell signaling, cell death, and other essential biological processes. Disruptions in ceramide metabolism have also been linked to the development and progression of cancer.When the team analyzed blood samples collected before treatment in both studies, they discovered differences in ceramide profiles between Black and white patients. Black patients had lower overall ceramide levels but higher levels of specific long-chain ceramides, which previous research has associated with worse cancer behavior.As Black patients received androgen receptor pathway inhibitor therapy, levels of potentially harmful long-chain ceramides decreased while levels of shorter-chain ceramides increased. White patients showed the opposite trend, with increases in long-chain ceramides and decreases in shorter-chain versions.Researchers also identified specific ceramide species that were associated with important clinical outcomes, including disease progression, radiographic progression-free survival, and overall survival. Notably, the ceramides linked to outcomes differed between Black and white patients.Together, these findings suggest that ceramide metabolism may contribute to how patients respond to hormone-based therapies.One of the most exciting potential implications of the research is the possibility that ceramides could serve as biomarkers—biological indicators that help predict how a patient is likely to respond to treatment.If validated in additional and larger patient populations, ceramide profiles could help physicians identify which patients are most likely to benefit from androgen receptor pathway inhibitors and potentially guide treatment decisions earlier during care."We can also start thinking about testing combinations of current hormone therapies with treatments that alter ceramide metabolism in models of prostate cancer in the research laboratory," Freedman said. "That approach could potentially improve outcomes even further."The work represents another example of how laboratory science and clinical research can work together to advance cancer care.Freedman credits the study's success to the close collaboration between translational scientists and clinical investigators, as well as the decision to integrate scientific research directly into the clinical trials.The next steps will include validating the findings in additional and larger patient groups and conducting additional studies to better understand how ceramides influence prostate cancer treatment response. Researchers also plan to explore in the laboratory whether targeting ceramide metabolism could enhance the effectiveness of existing therapies.Ultimately, the goal is to develop more precise treatment approaches and address longstanding disparities in prostate cancer outcomes."This is a great example of why it's important to build science into clinical trials," Freedman said. "Every time we learn more about the biology behind treatment response, we're creating opportunities to develop better tools, better therapies, and better outcomes for patients."
