BreakThroughs is produced twice per year by the DCI Office of Development. Learn how our researchers, physicians, nurses, patients, donors, and volunteers are working to change the rules on cancer. To support our breakthrough research and patient care, donate here.
Our Cover Story: When Prevention Pays Off.
After taking steps to stop a pre-cancer, Therese has written two books and exercises an hour and a half every day. Read the story on page 11. Cover photo by Aurora Rose De Crosta.
Our Cover Story
Duke Cancer Institute is celebrating 50 years of transforming cancer care and discovery as a comprehensive cancer center designated by the National Cancer Institute. Illustration by Ken Orvidas.
Our Cover Story: Setting Sights on a Cure.
Breast cancer patients have more treatment options than ever before, including a new one developed at Duke that is in clinical trials for advanced cancer (see page 13). One Duke researcher who helped lead the development of that drug thinks he can make even more progress by shifting gears to focus on enhancing the body's immune system (see page 8).
See more BreakThrough articles in our News section.
THIS FALL, WE WRAP UP OUR CELEBRATION OF DUKE’S 50 YEARS of transforming cancer discovery and care as a comprehensive cancer center. This issue of Breakthroughs highlights how we have revolutionized the field of stem cell transplant and improved outcomes for people with blood cancers. This field has also set the stage for promising new cancer-fighting immunotherapies, and as we look to the future, we envision more patients benefiting from the ability to engineer cells to make them better cancer killers and to target them to each individual. These are just a few of the innovations that you have made possible. You’ll also see featured in this issue a milestone approval of a new drug for advanced breast cancer, as well as one of our efforts to expand breast cancer care to our surrounding communities. I want to thank you — our donors and friends — for your continued partnership. Your willingness to stand beside us in the fight against cancer motivates us to continue pushing boundaries to discover, develop, and deliver tomorrow’s cancer care...today. Michael B. Kastan, MD, PhD Executive Director, Duke Cancer Institute Professor of Pediatrics William and Jane Shingleton Professor, Pharmacology and Cancer Biology
For decades, bone marrow transplantation has saved the lives of patients with blood cancers or other inherited or acquired bone marrow diseases. But today, it’s helping more people than ever because medical advances have made the procedure feasible for more patients. Bone marrow is spongy tissue in our bones that houses the blood stem cells that give rise to red blood cells, platelets, and the workhorses of the immune system, white blood cells. In a bone marrow transplant, stem cells from healthy bone marrow or blood are infused into a patient to do the work of producing blood cells. Patients with certain blood cancers like lymphoma may need a transplant if the chemo or radiation necessary to kill their cancer also kills their bone marrow. In other cases, the recipient’s bone marrow stem cells may be producing blood cells, but those cells aren’t up to the task of recognizing and killing cancer and need to be replaced with stem cells from a healthy donor. The transplanted cells can come from the patient (collected ahead of time) or from a donor. In the past, patients in need of a transplant had to have a matched donor, meaning that recipient and donor had the same immunologic proteins, called HLA. Otherwise, the donor cells would launch an immune attack on the recipient’s body. Over the last few decades, researchers have made significant progress in discovering how to perform transplants using donated cells that aren’t a perfect match. Furthermore, stem cells can now be harvested not just from bone marrow but from blood and umbilical cord. “More patients can benefit from transplantation now because there are more donor options,” said Edwin Alyea, MD, the chief medical officer of the Duke Cancer Institute. “And we can now offer reduced intensity transplants, with lower-dose chemotherapy, to patients who were previously not eligible because of age or other medical problems.”
In 2006, 12-year-old Kameron Kooshesh temporarily moved from California to Durham with his parents so that he could get a bone marrow transplant with Duke’s Joanne Kurtzberg, MD. He had just undergone three years of chemo for acute lymphocytic leukemia, and his cancer had returned. His mom researched pediatric bone marrow transplant programs nationwide and chose Duke for her son. Kooshesh quickly bonded with Kurtzberg and others on his team, from physicians to nurses to case managers. “They knew me and my family so well,” he said. “We trusted them as we would a family member. Duke felt like my home.” Kooshesh’s bone marrow transplant initially went well, but he developed severe graft versus host disease (GVHD) that didn’t respond to standard treatment. Kooshesh knew of some other kids who had died from GVHD and wondered if the end had come for him. >Kurtzberg was aware of a drug that might help, but it was still in clinical trials. She won a compassionate-use authorization from the Food and Drug Administration. “Just a couple of infusions of this drug, and I was cured,” he said, “truly cured.” Kooshesh believes he wouldn’t have gotten that drug if he’d been treated at another institution. “Dr. K. is absolutely unbelievable,” he said. “She has a mastery of basic science and clinical and translational medicine that few others have.” Kooshesh graduated from Harvard Medical School in 2022 and is now a resident in internal medicine at Massachusetts General Hospital. He plans to devote his career to improving stem cell transplants and reducing GVHD. “I now do the exact kind of research that served as the basis for the drug that saved my life,” he said.
Hannah Woriax, MD, assistant professor of Surgery, joined Duke in 2021, settling in her hometown of Pembroke, North Carolina, after completing residency at Virginia Tech’s Carilion School of Medicine and fellowship at the University of Alabama Birmingham. She returned to North Carolina with the goal of establishing a means of care and research for breast cancer patients in rural North Carolina communities. She practices at both the Gibson Cancer Center in Lumberton and the Scotland Cancer Treatment Center in Laurinburg, both part of the Duke Cancer Network. “The median income in this area is about $35,000, so quite a few patients do not have access to a full-time vehicle, and most people live at least 15-20 minutes away from wherever they’re being seen,” Woriax said. She works to establish a rapport with both her patients and her staff, communicating the importance of working with and around the patient’s means and abilities. Woriax’s journey into medicine was kick-started by watching her grandfather, former Navy corpsman and family medicine physician Frank Woriax, MD, who was the first Native American to graduate from the Duke University School of Medicine. The junior Dr. Woriax learned from her grandfather, whom she affectionately refers to as “papa,” the importance of giving back to their home community of rural and native North Carolinians. “I came home to practice here because I knew that our patients deserve just as much access to care as the patients that live in more urban areas. And I can be a voice for our patients in a different space,” Woriax said, emphasizing her own credibility to both her patients and the support of the Duke Health system. “I work here, I grew up here, and I live here now. I understand the way of life and challenges on a different level.” For Woriax, it is also important that care providers understand the historical nature of patient education in rural areas, particularly the lasting distrust for the medical community among the Native American and Black populations. “A lot of people here still see no difference in how we currently practice medicine and how experiments were conducted only decades ago,” she said. “So for me, for breast cancer patients specifically, I need to educate my patients on what their options are and why they would benefit from things like genetic testing, without any negative or malicious intent.” Being Lumbee herself helps Woriax further establish credibility and trust with her patients, several of whom have known her since she was a child. “I long for those meaningful and long-term relationships with my patients and their loved ones,” Woriax said. “I tell my patients every time I meet them, ‘Don’t worry, you won’t lose me. We’re in each other’s lives now.’” Woriax said that she hopes the Lumberton and Scotland locations will serve as prototypes for additional programs in the future. “Our goal is to identify where these gaps are and try to build a bridge for patients in a way that’s meaningful for them and long lasting and sustainable for the community.”
Ovester Grays, athletic director and head women’s basketball coach at Hillside High School in Durham, North Carolina, was diagnosed with mantle cell lymphoma in 2019. Through his nine months of treatment, his entire care team at Duke reassured him. “I was confident about the facts, but the emotional and the mental was nurtured every single step of the way. And it changed my life,” he said. “I’ve told my family if I’m every seriously sick, take me to Duke Hospital. They’re some of the best trained medical treatment personnel in the world. So they mean the world to me.”
When Alexa Balthazar was diagnosed with leukemia at age 28, she ultimately needed a bone marrow transplant. Knowing that her transplant physician, Mitchell Horwitz, MD, had a plan was very encouraging, but she still faced a whirlwind of emotions. Teen and Young Adult Oncology Program nurse navigator Jackie Balliot, BSN, RN, OCN, was there to help. She made several referrals, including connecting Alexa to medical family therapist Geoffrey Vaughn, LMFT, ATR. “What you go through is traumatic, and to be able to talk with someone who is not a family member or friend about very serious topics was helpful for me,” Balthazar said. In May 2023, she celebrated her one-year transplant birthday.
Research that originated in a Duke Cancer Institute (DCI) laboratory contributed to Food and Drug Administration (FDA) approval of the first new endocrine therapy for breast cancer since 2002, and the only drug designed to target mutations in estrogen receptor 1 (ESR1). Donald McDonnell, PhD, associate director For translational research at DCI and the Glaxo-Wellcome Distinguished Professor of Molecular Cancer Biology, directed the research team that led to the development of elacestrant (Orserdu, StemlineTherapeutics, Inc). The new therapy, a selective estrogen receptor down-regulator (SERD), is indicated for the treatment of postmenopausal women or adult men with estrogen-receptor-positive/HER2-negative ESR1-mutated advanced or metastatic breast cancer who have been treated unsuccessfully with at least one previous endocrine therapy. The FDA approved the therapy in January 2023.
After more than 30 years as a medical oncologistin her thriving practice in Newport News,Virginia, 1978 Duke University School of Medicinegraduate Elizabeth Harden, MD, sees cancer turninginto more of a chronic disease. “I used to have ashort relationship with patients. Now I have patientswho I’ve been seeing for 15 or 20 years who aredoing great,” she said. Harden’s husband, surgical oncologist RichardHoefer, DO, FACS, added, “If we can’t cure it, wecan contain it.” Harden sees her mentors and friends at Dukeas partners in that success. “Duke has beencomplimentary to us in our life’s work. We recognizethe value of having a very strong academic medicinecommunity as a resource,” she said. As Harden and Hoefer celebrated 35 years ofmarriage, and as Duke Cancer Institute marks 50years as a comprehensive cancer center, the coupleestablished an estate bequest to benefit futurephysicians and researchers.They worked closely with Duke Health’s giftplanning office and Executive Vice President forHealth Affairs and School of Medicine Dean MaryKlotman, MD, to create a gift that will benefitcancer, immunology, and graduate medicaleducation. Their bequest includes endowments for afull professorship and two associate professorships. “We don’t know what the next big frontier isin oncology, so we didn’t want to narrow it toone area,” Harden said. “We take great pride inknowing our estate will be used in this way.”
Duke alum Leslie Graves has known about Duke’s mission to provide life-changing cancer care since she was a teenager. Her father was a childhood friend of legendary cancer surgeon William Shingleton, MD, when the two were growing up in eastern North Carolina. In 1973, when Shingleton became the founding director of Duke Comprehensive Cancer Center (now known as Duke Cancer Institute), Graves’ father, John Graves, a Duke alum, began supporting the effort. “He felt like that it was such an incredible organization, and he talked to me about it,” Graves said. “He was super proud of his childhood friend.” She witnessed firsthand the compassionate care Duke provides when her father was treated for bladder cancer. “He felt they took really great care of him, extended his life, and honored his wishes about his treatment,” Graves said. He sadly lost his battle with the disease in 2009. Graves serves as treasurer of the Fibromalellar Cancer Foundation, and in 2017 she joined the Duke Cancer Institute Board of Advisors. She served as vice-chair for four years, and in 2022 she began serving as chair. In October 2022, Graves received the William W. Shingleton Award, the highest honor given to friends of Duke Cancer Institute.
As Duke celebrates more than 50 years of cancer breakthroughs, a new research program works toward a future when no one ever develops cancer.
In 2016, when Pat Smith first felt a lump on her thigh, she didn't think much about it. But a “just-in-case” MRI led to a biopsy, and then her doctor told her it was a leiomyosarcoma — an aggressive, cancerous tumor. Smith, who lives in Florida, had never heard of a leiomyosarcoma, and for good reason. They are rare, as are all sarcomas (soft tissue cancers). Leiomyosarcomas grow in the smooth muscles, which are in the hollow organs of the body, such as the intestines, stomach, bladder, and blood vessels. Smith had gone to the appointment alone because she wasn’t expecting her biopsy results so soon. Stunned, she went home to tell her husband, Randy, and to call her three adult children. Her son impressed upon her that because leiomyosarcomas are so rare, she should get treatment at a center that sees a lot of these types of tumors. Then she remembered that her good friend Andrea Erwin is retired from Duke University and volunteers at Duke Cancer Center. Erwin arranged for someone from Duke to call her that same afternoon. As it turned out, Duke has a team of 25 specialists focused on sarcomas. Smith had an appointment scheduled in two weeks with David Kirsch, MD, Barbara Levine University Distinguished Professor, and Brian Brigman, MD, professor of orthopaedic surgery, and other providers. “The greatest thing is that when I met each one of them, no one rushed me,” Smith said. “And they all said, ‘What do you know about your particular type of tumor?’ And they all explained it, and it was like they had all the time in the world,” Smith said. When she was first diagnosed, she remembers thinking “Why me?” Then she prayed about it. “I said to myself, ‘Pat, God has this. You’ve found a great place to go, and they’re going to take care of you, and you’re going to have a positive attitude.’” Smith started keeping a “blessings list,” naming all the positive things about her cancer experience. “You really can meet a lot of great people,” Smith said. “I’m originally from North Carolina, and I have connected with old friends.” Smith had radiation every day for several weeks, staying with her friend Andrea. A month later, she had surgery. She is now considered cancer free, though doctors at Duke watch her closely. Every three months, she has a CT scan of her lungs, because that’s where this tumor tends to spread. She also has a yearly MRI of her leg. Smith prefers to come to Duke for those screenings. “I chose to come back to Duke because this is the best place to take care of me,” she said during a visit to Duke Cancer Center. “I walk in that front door down there, and I feel this peace wash over me.” Since her diagnosis, Smith has welcomed two grandchildren, and she enjoys taking them to the beach. In November 2022, she and her husband, Randy, will celebrate 40 years of marriage.
Pancreatic cancer is one of the most challenging types because it is most often diagnosed in the late stages, when surgery isn’t possible. In 2022, the five-year survival rate for the disease is 11%, a slight increase from last year, according to the American Cancer Society. To make outcomes better, researchers around the world are trying to find a marker from blood or some other bodily fluid that would reliably diagnose pancreatic cancer in its early stages, said Jim Abbruzzese, MD, Duke Cancer Institute Distinguished Professor of Medical Oncology. Abbruzzese sees promise in a test that has been studied in the lab of Chris Counter, PhD, George Barth Geller Distinguished Professor of Pharmacology. Abbruzzese and hematology/oncology fellow Ryne Ramaker, MD, PhD, are beginning work to translate it to patients. Counter’s lab tries to capture the moment when a normal cell progresses to a tumor, then study it. Even in a cancer with lots of successful treatment options, like melanoma, the best bet is still finding the disease early, said Counter, whose mother-in-law Linda Woolfenden died of melanoma. It’s even more important in a challenging disease like pancreatic cancer. Siqi Li, PhD, now a Damon Runyan fellow at Fred Hutchinson Cancer Research Center, was a PhD student in Counter’s lab when she became intrigued by a method called maximum-depth sequencing, which was developed by researchers in the lab of Evgeny Nudler, PhD, at New York University to detect mutations that lead to antibiotic resistance in bacteria. “Siqi saw the parallels between bacteria and cancer, and she was very interested in using this assay in mammals,” Counter said. “So she adapted this assay with the help of the lab of Dr. David McAlpine here at Duke for the mammalian genome to capture mutations causing cancer.” Counter’s team found that this technology captures mutations that are too few and far between to be detected by traditional next-generation gene sequencing. “The assay was so sensitive, that Siqi was able to detect a cancer-causing mutation a week after mice were exposed to an environmental carcinogen,” Counter said. The team published results of this work in 2020 in the journal Nature Communications and in 2022 in the journal eLife. The studies were supported in part by a Duke Cancer Institute pilot grant, a program sustained by donor funds. The test holds promise not only because of its sensitivity, but also because it’s specific to KRAS, a gene commonly mutated in pancreatic cancer, Abruzzese said.