DCI Board of Advisors member Nancy Wright during a visit to Duke in August 2021. Photo by Les Todd.
Stronger by the Day
Published
From the Duke Cancer Institute archives. Content may be out of date.
In 1988, Nancy Wright successfully beat breast cancer. But at the time, she didn’t know any other cancer survivors. “Nobody talked about cancer back then. I realize just how uneducated I was about cancer in general,” she says.
Her mother-in-law, who was a member of a group that existed at the time called the Duke Cancer Institute (DCI) Citizens Advisory Council, arranged for a two-time breast cancer survivor to speak to a group near Wright’s home in Lexington, NC.
Shortly after that, in 1994, Wright joined the DCI Citizens Advisory Council, then later the DCI Board of Advisors. She found it exciting and educational to hear from other survivors and cancer researchers. “The council encouraged us to be advocates and to write letters to our legislators asking for increased funding for cancer research,” she says. “That was my first foray into political activism.”
Nancy began thinking of herself as someone who advocated for others with cancer. Patients should ask lots of questions about their care, and they should expect answers, she says. She advocated for her husband as he successfully fought lymphoma with Duke’s help, and she has advised countless friends and family.
She has always told her friends to go to Duke for cancer care because of the access to the latest evidence-based treatments and new therapies available through clinical trials. “If not Duke, go to one of the three National Cancer Institute-designated comprehensive cancer centers in North Carolina. We’re fortunate to have three. Some states don’t have any,” she says.
A Heart-Dropping Diagnosis
In February 2021, Nancy had to follow her own advice. One morning she woke up jaundiced. She felt fine, but consulted with her primary care doctor. Results of her blood tests were normal, but her liver values were elevated.
When subsequent tests showed her liver values had worsened, her doctor ordered a CT scan.
The scan showed a tumor in her pancreas. ”Well, my heart just went through the floor,” Nancy says. “I thought, besides glioblastoma, I can’t have anything worse.”
The cancer was stage 2. Duke surgeon Peter Allen, MD, performed surgery right away. Nancy needed the Whipple procedure, a complex operation to remove parts of the pancreas, the small intestine, gall bladder, and stomach, then reattach the remaining portions so they can function.
“Dr. Allen was so very positive, and he reassured me,” Nancy says. The surgery went well. She didn’t have a lot of pain, and the 10-day recovery was easier than she expected.
The treatment afterward was the challenging part for her. She could tolerate only four weeks of the planned eight-week chemotherapy regimen. She lost more than 50 pounds.
She hadn’t realized how weak she had become. “It was all I could do to leave the cancer center and walk to the parking deck,” she says. “When I was at my worst, Gordon had to help me up those three steps. I did not have the strength to get up the steps, and it really surprised me.”
Nancy has worked through it with the help of her husband of 52 years. She feels stronger now, able to climb the stairs leading to their beach home without stopping to rest. She is cooking and enjoying some of her favorite foods again, like fresh summer corn. Listening to the waves is its own form of therapy.
“Right now, I am in a holding pattern of recovering strength, gaining weight, and eating,” she says.
Once she is stronger, she hopes to work with her oncologist, James Abbruzzese, MD, to try a different treatment regimen tailored to her. “As anxious as I am about not being treated right now, because I know how aggressive pancreatic cancer is, I also know that my team has my best interests at heart,” she says.
Friends who have been treated elsewhere have told her that sometimes they felt their doctors weren’t listening to them. She has found the opposite at Duke. “Dr. Abbruzzese has been really good about answering my questions,” she says.
Nancy is optimistic about the future, including the hope of defeating all cancer if young researchers are supported. The Wrights’ granddaughter, Elyse, has an interest in science and cancer research, and she interned in the lab of Duke cancer researcher Jason Somarelli, PhD, during her junior year of high school. She is now a sophomore at UNC-Chapel Hill and is working in the lab of a cancer researcher there.
Elyse credits Somarelli with encouraging her passion for research. “Dr. Somarelli valued my thoughts and questions, and he was the first person to really challenge my thinking and push me to think more critically,” she says.
“You cannot foster an interest in research early enough,” Nancy says. “As my granddaughter says, ‘Why can’t I be the one to discover a cure for cancer?’ You have to love the passion and optimism of youth.”
A new Duke-led research study reveals groundbreaking insights into the mechanisms behind immunotherapy resistance in melanoma and colon cancer. Nicholas DeVito, MD, a Duke Cancer Institute medical oncologist specializing in gastrointestinal cancer, helped lead the research team in this work.The findings published in Cancer Research focus on the variability in patient responses to immunotherapy and the role of epithelial-mesenchymal transition (EMT) in this process. Despite the benefits of immunotherapy for approximately half of melanoma patients, the underlying mechanisms of resistance remain unclear."Not all patients with melanoma respond to immunotherapy, even though about half of them benefit from it, and most patients with colon cancer do not have a response at all” DeVito said. “Because of that, there's a question of, what is the mechanism behind that?"The team focused this research on the Hedgehog pathway, particularly the transcription factor GLI2, which they found plays a crucial role in immunotherapy resistance. The Hedgehog pathway, typically active during embryonic development, was shown to be associated with invasive and EMT in melanoma.The research revealed that GLI2 regulates two immunosuppressive pathways: the Wnt pathway and the prostaglandin pathway. These pathways are meant to help wounds heal, but tumors use GLI2 to activate pathways that have an immune suppressive influence on the microenvironmentUsing mouse models and patient samples, the team demonstrated that activation of GLI2 in cancer cells leads to immunotherapy resistance. They employed various techniques, including flow cytometry, single cell RNA sequencing, and chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) to uncover the role of GLI2 in regulating immunosuppressive pathways.These findings suggest that inhibiting specific prostaglandin receptors can prevent immunotherapy escape, and blocking Wnt secretion can restore tumor control after immunotherapy escape, offering potential therapeutic strategies for patients.“If you had a high GLI2 signature in a tumor, there was a more than 75 percent chance that the patient is not going to respond to immunotherapy,” DeVito said. “The drugs that we've used in our mouse studies are all ones that have been used in humans, so they could be easily paired with a GLI2-based biomarker in clinical trials.”By identifying patients with high GLI2 signatures, clinicians can tailor treatments to improve outcomes. This approach is particularly relevant for colon cancer patients, who often exhibit primary resistance to immunotherapy.DeVito hopes to explore the role of GLI2 in colon cancer, particularly in patients with liver metastasis, and further develop biomarkers for combination treatments in this disease. His team is investigating how GLI2-mediated pathways contribute to immunotherapy resistance and spread to the liver by generating an immune-suppressive microenvironment, or ‘home’ for cancer outside the colon. The team is acquiring patient specimens and working with Jatin Roper, MD, assistant professor of medicine in the Duke Department of Medicine, to implement an advanced colon cancer mouse model that better represents human disease.“Immunotherapy is more tolerable and works better and longer than chemotherapy does,” DeVito said. “Using biomarkers, we can have an idea what the molecular pathways driving the immune landscape in the tumor are and can target those pathways in specific patients to improve the effectiveness of existing immunotherapies. Developing the ability to identify which immunosuppressive pathways are active in one tumor and not another also helps us not expose patients without those biomarkers to unnecessary treatments.”
A new Duke-led research study reveals groundbreaking insights into the mechanisms behind immunotherapy resistance in melanoma and colon cancer. Nicholas DeVito, MD, a Duke Cancer Institute medical oncologist specializing in gastrointestinal cancer, helped lead the research team in this work.The findings published in Cancer Research focus on the variability in patient responses to immunotherapy and the role of epithelial-mesenchymal transition (EMT) in this process. Despite the benefits of immunotherapy for approximately half of melanoma patients, the underlying mechanisms of resistance remain unclear."Not all patients with melanoma respond to immunotherapy, even though about half of them benefit from it, and most patients with colon cancer do not have a response at all” DeVito said. “Because of that, there's a question of, what is the mechanism behind that?"The team focused this research on the Hedgehog pathway, particularly the transcription factor GLI2, which they found plays a crucial role in immunotherapy resistance. The Hedgehog pathway, typically active during embryonic development, was shown to be associated with invasive and EMT in melanoma.The research revealed that GLI2 regulates two immunosuppressive pathways: the Wnt pathway and the prostaglandin pathway. These pathways are meant to help wounds heal, but tumors use GLI2 to activate pathways that have an immune suppressive influence on the microenvironmentUsing mouse models and patient samples, the team demonstrated that activation of GLI2 in cancer cells leads to immunotherapy resistance. They employed various techniques, including flow cytometry, single cell RNA sequencing, and chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR) to uncover the role of GLI2 in regulating immunosuppressive pathways.These findings suggest that inhibiting specific prostaglandin receptors can prevent immunotherapy escape, and blocking Wnt secretion can restore tumor control after immunotherapy escape, offering potential therapeutic strategies for patients.“If you had a high GLI2 signature in a tumor, there was a more than 75 percent chance that the patient is not going to respond to immunotherapy,” DeVito said. “The drugs that we've used in our mouse studies are all ones that have been used in humans, so they could be easily paired with a GLI2-based biomarker in clinical trials.”By identifying patients with high GLI2 signatures, clinicians can tailor treatments to improve outcomes. This approach is particularly relevant for colon cancer patients, who often exhibit primary resistance to immunotherapy.DeVito hopes to explore the role of GLI2 in colon cancer, particularly in patients with liver metastasis, and further develop biomarkers for combination treatments in this disease. His team is investigating how GLI2-mediated pathways contribute to immunotherapy resistance and spread to the liver by generating an immune-suppressive microenvironment, or ‘home’ for cancer outside the colon. The team is acquiring patient specimens and working with Jatin Roper, MD, assistant professor of medicine in the Duke Department of Medicine, to implement an advanced colon cancer mouse model that better represents human disease.“Immunotherapy is more tolerable and works better and longer than chemotherapy does,” DeVito said. “Using biomarkers, we can have an idea what the molecular pathways driving the immune landscape in the tumor are and can target those pathways in specific patients to improve the effectiveness of existing immunotherapies. Developing the ability to identify which immunosuppressive pathways are active in one tumor and not another also helps us not expose patients without those biomarkers to unnecessary treatments.”
