The Duke Cancer Institute has received the Notice of Award for the renewal of its Cancer Center Support Grant (CCSG) from the National Cancer Institute (NCI), providing funding and reaffirming its position as one of the premier cancer centers in the United States.
This recognition underscores the quality and impact of the research, patient care, education, and outreach efforts facilitated by the DCI.
Throughout the last CCSG funding period, the DCI has seen an overall increase in high-impact publications and grant funding, specifically by the National Cancer Institute (NCI). The DCI has also increased its clinical trial enrollments, including a 47 percent increase in interventional accruals and a 10 percent increase in therapeutic accruals.
Significant scientific highlights from the previous funding period were many, but included:
The discovery reported in the journal, Nature, by Chuan-Yuan Li, PhD, that PCSK9 inhibition augments the effectiveness of immunotherapies, leading to currently ongoing clinical trials led by Scott Antonia, MD, PhD, co-leader of the DCI Immuno-Oncology program and director of the DCI Center for Cancer Immunotherapy;
A multi-institutional clinical trial testing new targeted therapies for pancreatic cancer published in the New England Journal of Medicine, led by John Strickler, MD, medical oncologist for the DCI Gastrointestinal Cancer disease group and co-leader of the DCI Precision Cancer Medicine and Investigational Therapeutics program; and
A multi-center clinical trial led by Daniel George, MD, co-chair for the DCI Center for Prostate and Urologic Cancers, that demonstrated an unexpectedly effective treatment regimen for black men with metastatic prostate cancer.
“The CCSG renewal is a testament to our collective strength and shared commitment to making significant strides in the fight against cancer,” said Michael Kastan, MD, PhD, executive director for the DCI. “This provides a strong foundation for continued growth and impact in the years to come.”
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."
For decades, a diagnosis of metastatic breast cancer has carried a clear message: while treatments can help control the disease and extend life, the disease is generally considered incurable. As a result, treatment strategies have traditionally focused on managing cancer and maintaining quality of life rather than pursuing a cure.New advances in breast cancer therapies are changing that conversation. Research led by Duke Cancer Institute breast surgical oncologist Jennifer Plichta, MD, suggests that some patients with limited metastatic breast cancer may benefit from a more aggressive treatment approach than has traditionally been offered. The findings, published in JAMA Surgery, add to growing evidence that metastatic breast cancer is not the same for every patient and that treatment decisions may need to become more personalized.Plichta's research builds on years of work focused on improving how physicians classify and predict outcomes for patients with breast cancer. Historically, a diagnosis of metastatic, or stage IV, breast cancer, was associated with poor survival. However, the development of targeted therapies and other advances in systemic treatment have dramatically improved outcomes for many patients."Many women with metastatic breast cancer are now living for years and sometimes even a decade after diagnosis," Plichta said. "We've come a long way in terms of treatment options and survival."At the same time, researchers have discovered significant variation among patients with metastatic disease. Some experience aggressive cancer that progresses quickly, while others have relatively limited disease that remains controlled for long periods.This variability led Plichta and her colleagues to ask an important question: Are there certain patients with metastatic breast cancer who could benefit from treatment strategies typically reserved for patients with earlier-stage disease?The study focused on patients with what is known as oligometastatic breast cancer, a form of metastatic disease in which cancer has spread to only a limited number of sites. Researchers believe this group may represent a distinct subset of patients whose disease behaves differently than widespread metastatic cancer.Using data from the National Cancer Database, which captures information on many newly diagnosed breast cancers in the U.S., the team analyzed outcomes among patients with limited metastatic disease. They examined whether patients received treatment directed at the primary breast tumor, treatment directed at metastatic sites, both treatments, or neither.The goal was to determine whether a treatment approach that more closely resembles care for stage III breast cancer—combining systemic therapy with aggressive local treatment—might improve outcomes for selected patients."What stood out was that removing the primary breast tumor seemed to be the factor most strongly associated with improved survival," Plichta said. "Treating the distant sites did not appear to offer the same survival advantage on its own."While previous studies have explored surgery for patients with metastatic breast cancer, results have been mixed. Plichta believes one reason may be that metastatic breast cancer is often treated as a single category, even though patients can have vastly different disease characteristics and prognoses.One of the most significant implications of this research is how clinicians think about treatment goals. Patients with stage III breast cancer are typically treated with curative intent, meaning doctors use every appropriate therapy available, including chemotherapy, surgery, and radiation, in an effort to eliminate the disease. Patients with metastatic breast cancer, by contrast, are usually treated with palliative intent, focusing on disease control rather than cure.But as outcomes improve, the line between those groups may not be as clear as it once was."We're seeing some patients with metastatic disease living longer than patients with locally advanced breast cancer," Plichta said. "That raises important questions about whether some patients with limited metastatic disease should be approached differently."Because the study was retrospective, the results point to an important association that warrants further study. Several clinical trials are now being developed to investigate curative-intent treatment strategies in specific subgroups of metastatic breast cancer patients, including those with HER2-positive disease. Duke hopes to participate in these multi-institutional studies as the field continues to evolve.As breast cancer treatments continue to improve, researchers are gaining a more nuanced understanding of metastatic disease. For Plichta, the study represents an important step toward that goal."I hope this work encourages further research into which patients may benefit from a curative-intent approach," she said. "The ultimate goal is to find the right treatment strategy for the right patient."
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."
For decades, a diagnosis of metastatic breast cancer has carried a clear message: while treatments can help control the disease and extend life, the disease is generally considered incurable. As a result, treatment strategies have traditionally focused on managing cancer and maintaining quality of life rather than pursuing a cure.New advances in breast cancer therapies are changing that conversation. Research led by Duke Cancer Institute breast surgical oncologist Jennifer Plichta, MD, suggests that some patients with limited metastatic breast cancer may benefit from a more aggressive treatment approach than has traditionally been offered. The findings, published in JAMA Surgery, add to growing evidence that metastatic breast cancer is not the same for every patient and that treatment decisions may need to become more personalized.Plichta's research builds on years of work focused on improving how physicians classify and predict outcomes for patients with breast cancer. Historically, a diagnosis of metastatic, or stage IV, breast cancer, was associated with poor survival. However, the development of targeted therapies and other advances in systemic treatment have dramatically improved outcomes for many patients."Many women with metastatic breast cancer are now living for years and sometimes even a decade after diagnosis," Plichta said. "We've come a long way in terms of treatment options and survival."At the same time, researchers have discovered significant variation among patients with metastatic disease. Some experience aggressive cancer that progresses quickly, while others have relatively limited disease that remains controlled for long periods.This variability led Plichta and her colleagues to ask an important question: Are there certain patients with metastatic breast cancer who could benefit from treatment strategies typically reserved for patients with earlier-stage disease?The study focused on patients with what is known as oligometastatic breast cancer, a form of metastatic disease in which cancer has spread to only a limited number of sites. Researchers believe this group may represent a distinct subset of patients whose disease behaves differently than widespread metastatic cancer.Using data from the National Cancer Database, which captures information on many newly diagnosed breast cancers in the U.S., the team analyzed outcomes among patients with limited metastatic disease. They examined whether patients received treatment directed at the primary breast tumor, treatment directed at metastatic sites, both treatments, or neither.The goal was to determine whether a treatment approach that more closely resembles care for stage III breast cancer—combining systemic therapy with aggressive local treatment—might improve outcomes for selected patients."What stood out was that removing the primary breast tumor seemed to be the factor most strongly associated with improved survival," Plichta said. "Treating the distant sites did not appear to offer the same survival advantage on its own."While previous studies have explored surgery for patients with metastatic breast cancer, results have been mixed. Plichta believes one reason may be that metastatic breast cancer is often treated as a single category, even though patients can have vastly different disease characteristics and prognoses.One of the most significant implications of this research is how clinicians think about treatment goals. Patients with stage III breast cancer are typically treated with curative intent, meaning doctors use every appropriate therapy available, including chemotherapy, surgery, and radiation, in an effort to eliminate the disease. Patients with metastatic breast cancer, by contrast, are usually treated with palliative intent, focusing on disease control rather than cure.But as outcomes improve, the line between those groups may not be as clear as it once was."We're seeing some patients with metastatic disease living longer than patients with locally advanced breast cancer," Plichta said. "That raises important questions about whether some patients with limited metastatic disease should be approached differently."Because the study was retrospective, the results point to an important association that warrants further study. Several clinical trials are now being developed to investigate curative-intent treatment strategies in specific subgroups of metastatic breast cancer patients, including those with HER2-positive disease. Duke hopes to participate in these multi-institutional studies as the field continues to evolve.As breast cancer treatments continue to improve, researchers are gaining a more nuanced understanding of metastatic disease. For Plichta, the study represents an important step toward that goal."I hope this work encourages further research into which patients may benefit from a curative-intent approach," she said. "The ultimate goal is to find the right treatment strategy for the right patient."
