Duke University Marching Band Kicks Off the DCI 50th Celebration (photo by Drawbridge Media)
At DCI 50th Celebration, the Sounds of Hope
Published
From the Duke Cancer Institute archives. Content may be out of date.
ONCOLOGY NURSE LEADERS Jennifer Loftis, MSN, RN, AOCNS, NEA-BC; Jennifer Frith, MSN, RN, OCN, NE-BC and Kerri Dalton, MSN, RN, AOCNS. (photo by Drawbridge Media)
On Thursday, April 14, 2022, Duke Cancer Institute clinical providers, researchers, staff, and leadership came together to celebrate the 50th anniversary of the Duke Comprehensive Cancer Center (now called Duke Cancer Institute).
As the DCI 50th kickoff celebration was gearing up on the grassy circle in front of Duke Cancer Center building in Durham, a few patients stopped by the adjacent Seese-Thornton Garden of Tranquility for some respite.
A breast cancer patient of Susan Dent, MD, braced for a long day of chemotherapy infusions. A man with stage 3 melanoma, being treated by Brent Hanks, MD, chatted in the shade of a tree with his wife ahead of his next appointment. A woman on her way to the Duke South clinics, meanwhile, shared her worries over her brother’s recent esophageal cancer diagnosis, their strong family history of cancer, and the importance of keeping up with her mammograms.
Joe Moore, MD — who hung up his DCI lab coat in 2019 after a 44-year Hematology /Oncology career — was admiring the newly-installed Sound of Hope bell (a gift of the J. Gordon Wright family in honor of Nancy Wright, a pancreatic cancer survivor) before Jana Wagenseller, RN, escorted him across the grass to a front-row seat, stage right. (Moore had begun his medical career at Duke in 1975 as a fellow and Wagenseller had begun her nursing career at Duke in 1976 and served in multiple leadership roles before retiring in 2004).
The Duke University Marching Band made a jubilant entrance onto the green and briefly performed in front of a big-screen slideshow showcasing moments in DCI history before the official program began.
Michael B. Kastan, MD, PhD, executive director of DCI (photo by Drawbridge Media)
Executive director of DCI Michael B. Kastan, MD, PhD, began by thanking the “spirited” band and welcoming the more than 500 attendees. He asked for a round of applause “for all of the talented and dedicated staff, physicians and researchers and residents who give our patients hope every single day,” then turned his focus to DCI’s thousands of patients, past and present.
“Though we’re celebrating many successes over the last 50 years, not every story is a success,” he said. “We’ve lost a lot of patients, family, and friends over the years. And I’d like to take a moment of silence so we can think about them as we move forward.”
In addition to celebrating the 50th anniversary of Duke’s recognition as a National Cancer Institute-designated Comprehensive Cancer Center, Kastan also recognized the ten-year anniversary of the stand-alone Duke Cancer Center building and the creation of the Duke Cancer Institute.
For this, he commended the leadership and direction of Victor Dzau, MD (a Duke cardiologist and pathologist who served as chancellor of Health Affairs from 2004 to 2014), Dean Emerita of the Duke University School of Medicine Nancy Andrews, MD, PhD (Pediatrics and Pharmacology & Cancer Biology), and Bill Fulkerson, Jr., MD, MBA, who served for the past 10 years as executive vice president of DUHS before stepping down in December.
“With his unwavering commitment to the DCI’s growth and care of our patients, I am proud to recognize Dr. Fulkerson among our attendees here today,” said Kastan, giving a nod to the pulmonologist who began his clinical career at Duke nearly 40 years ago. “Today we continue in our commitment to making innovative discoveries developing new ways to prevent, diagnose, and treat cancer and deliver those therapies in a patient-centric and family-centric way.”
GATHERINGS photo #2: Craig Albanese, MD (DUHS), Carey Anders, MD (Breast Oncology) & Andrew Berchuck, MD (Gynecologic Oncology) photo #3: Jie Wang, MD and Guiyun Zhou, NP, AOCNS, DNP (Hematologic Malignancies & Cellular Therapy) photo #4: lymphoma survivor Ovester Grays, Nolan Miller, MHA (Duke Sarcoma Center, Endocrine Neoplasia, Head & Neck Oncology, Skull Base Tumor Program) and Karen Kharasch (DCI Research Strategy & Operations) (photos by Drawbridge Media)
“Everybody in academic medicine knows about the DCI. It’s legendary,” said executive vice president of DUHS Craig Albanese, MD, who took the podium after Kastan. “There’s so much to be proud of in the last 50 years — the research, the training, the breakthrough treatments, and the exceptional cancer support services.”
Albanese also singled out the DCI’s thriving community partnerships.
“Our strategic work with community organizations is critical. It’s part of our mission. It’s fundamental to the fabric of the organization. We should be proud of that,” he said. “The DCI’s Community Outreach, Engagement, and Equity program is a national leader in addressing inequities in prevention and treatment through health education, cancer screening for early detection, and ensuring that people have access to primary care. And as a health system, our focus is on health equity, not just because it’s the right thing to do, but because it’s really critical for the health of our community. And in fact, it’s critical for the health of our nation. So, let’s all extend our gratitude towards those who do this profound and meaningful work.”
“What do I see for the future? It’s going to be a different future, a future based largely on automation, digital health, genomic studies, personalized care,” predicted Albanese, a seasoned healthcare executive and distinguished academic pediatric surgeon. “But in the end, it is compassion, empathy, patient experience, access, and community advancement that’s going to continue to make us who we are and make us unique…Certainly, if the last 50 years are any indication, I can’t wait to see what the next 50 years will bring.”
Mary Klotman, MD, dean of the Duke University School of Medicine, rounded out the speakers’ program with a deeper dive back in time. She traced the history of cancer care and research back to 1937 when one of the first brain tumor centers in the country was founded (Preston Robert Tisch Brain Tumor Center), and to 1947 when the first training program for medical students focused on clinical cancer care was established — all decades before the NCI designation.
And she noted key research milestones:
1950: Duke professor Joseph Beard, MD, received a grant from the American Cancer Society. Through that work, he and his team at Duke were one of the two groups to first report evidence of viruses in association with human leukemia.
1964: Bill Joklik, D.Phil (Oxford) was the first to examine the mechanism of action of interferon — the first cytokine to be recognized — in molecular terms.
1994: Duke scientists helped discover the BRCA1 and BRCA2 genes responsible for many inherited forms of breast and ovarian cancers.
2018: A genetically modified poliovirus therapy developed at DCI showed significantly improved long-term survival for patients with recurrent glioblastoma
Dean Mary Klotman, MD (photo by Drawbridge Media)
Klotman also highlighted the construction, in 1994, of two new buildings dedicated to research (the LSRC and the MSRB), the creation of the DCI in 2012, and the more recent founding of the pioneering Duke Center for Brain and Spine Metastasis that received critical support from Chancellor Eugene Washington’s Translating Duke Health Initiative.
“Whether you’re a researcher, physician, provider, patient, or trainee, I truly believe there is no better place to fight cancer than at Duke,” Klotman said. “Thank you all for what you do every day.”
Read Their Stories of Survival in Their Own Words
Stealing the show, were three cancer survivors invited to take the stage — each telling their personal, impactful, Duke Cancer story to thunderous applause before being joined by their care teams in touching on-stage reunions.
OVESTER GRAYS
30-year Athletic Director & Women’s Basketball Coach, Hillside High School, Durham, NC, 3-YEAR Survivor, Kidney Cancer and Mantle Cell Lymphoma
Ovester Grays and his care team (photo by Drawbridge Media)
“In March and April 2019, I was diagnosed with late-stage lymphoma. I want you to know that my panic and anxiety lasted about two minutes. And that was in prayer. And my God let me know that I was healed for a greater cause. But then, in the next five minutes, I was calling the Cancer Center.
Over the next few weeks of tests and discoveries and figuring out the best treatment, for me as a coach (there were) three things — physical, mental, and emotional. The cancer for me was the physical (part). I had to immediately treat the emotional. As I walked my way through these halls, all the tests — whether it was the lab or the radiologist, this test and that test — and while I had confidence in the physical science that Duke has here, I was reassured that my confidence would be reinforced every step of the way.
I was asked who in the hospital made the biggest difference, but with cancer, it’s every kind word, every word of understanding, every word of compassion. Every single individual I met from day one to nine months later after inpatient chemo reassured me. 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. My life has been dedicated to helping young people reach their goals. As I walk these halls my purpose has changed, and that’s to help all families and all communities endure an incredible journey.
So, thanks to all! I don’t know all the names. The leader was Dr. (Jie) Wang, but there was a tremendous team that made it all happen. So, I wanted to take a second to say thank you for the nurturing, thank you.”
REUNITED: DCI Hematologic oncologist Jie Wang, MD, and her patient Ovester Grays catch up at the DCI 50th Anniversary kickoff. Grays, Athletic Director & Women’s Basketball Coach at Hillside High School in Durham for the past 30 years, was diagnosed with kidney cancer and late-stage mantle cell lymphoma three years ago — according to Wang, “a double whammy.” Mantle cell lymphoma is a rare subtype of non-Hodgkin lymphoma; making up less than 10% of cases. Wang said Grays underwent successful partial resection of his kidney tumor, before she and his care team treated him with chemotherapy, as a hospital inpatient, for the lymphoma. “It generally has a pretty aggressive clinical course,” said Wang. “Ovester was always so chill. He’s so relaxed. We also got him on a clinical trial because we knew that it was going to be beneficial for him. We got him feeling a lot better quite quickly.” Wang joined the DCI faculty in 2018 after completing hematology/oncology fellowship training and earning
ELLE CHARNISKY
Mother of two, advocate, 6-year Survivor, Stage 4 Colorectal Cancer
Elle Charnisky and her care team (photo by Drawbridge Media)
Colorectal cancer survivor Elle Charnisky accepts a DCI gift basket of thanks from the executive director of DCI, Michael B. Kastan, MD, PhD. A rolling slideshow in the background reflects a photo of attendee Bill Fulkerson, Jr., MD, MBA, former executive vice president of DUHS who Kastan had thanked earlier in the day for his "unwavering commitment to the DCI’s growth and care of our patients." (photo by Drawbridge Media)
“I wanted to say thank you to all of you for your speeches. That was wonderful. So great to hear that information. My name is Elle Charnisky. I was diagnosed with stage four metastatic colorectal cancer in April 2016 with metastasis to my liver and both lungs at age 36. My husband Mike, you’re my rock. And we celebrate our 15th wedding anniversary this fall. And our kids Molly — who is here with me today — and Grant were one and four at the time. I endured the very harsh standard first and second line chemo at Siteman in St. Louis, for a little over a year, until just as it seemed we were running out of options, my second opinion doc, Dr. Nancy Kemeny at Memorial Sloan Kettering Cancer Center in New York, turned our worlds upside down and referred me here to the Duke Cancer Center.
When we sat down in the office of Dr. John Strickler, who is truly one in a million, we had a sense that our lives were never going to be the same. I think Dr. Strickler was trying to give us that sense and he was not wrong. He was the principal investigator of a new up and coming targeted therapy clinical trial for colorectal cancer patients with a strong HER 2 amplification, known as the Mountaineer trial. That trial, by the grace of God gave me my life back. That very first treatment I remember feeling like I wasn’t even on treatment at all. After my first scans since having started the trial, I remember Dr. S as I like to call him bringing up the impressive results and saying, ‘And I don’t think we’re done taking a sledgehammer to it yet.’ And he was right.
It kept the disease in full remission for nearly three years. Being a metastatic cancer patient, I had never been eligible for surgery up until that point, but the Mountaineer trial got me to where I was. My incredible team of doctors and nurses here at the Duke Cancer Center, doctors Manisha Palta, Julie Thacker, and Sabino Zani to name a few, reevaluated my case and deemed me eligible to have the lifesaving surgeries I needed.
I was even able to continue on with the Mountaineer trial for some time after those surgeries and had continued success on the trial until April of last year. And to this day, amazingly, I’m on a very similar targeted therapy regimen with no adverse side effects and full quality of life.
My time here at the Duke Cancer Center has been second to none, from the peaceful serene atmosphere — my favorite is when they play Ave Maria on the grand piano at the basement level — to the incredible nursing staff and counselors. I have to give a shout-out to Evan Dropkin, Leighanne Hartman, and Tracy Berger, and the research team of doctors. I truly cannot imagine it not being a part of my life. So, I would love to invite my team of care providers to come join me on the stage. Thank you so much!”
JOHN SANDERS
Father of five and Baptist pastor in Augusta, Georgia, 4-Year Survivor, Stage 2 Pancreatic Cancer
John Sanders and his care team (photo by Drawbridge Media)
John Sanders (photo by Drawbridge Media)
“I’m grateful, humbled, and honored to have been asked to participate. First of all, I just want to say that I got here at Duke by divine intervention. What I mean by this is (that) I had an initial opinion back in Augusta, Georgia. My name is John Sanders. I got so excited, I didn’t tell you my name, but that’s ok.
So, I went to the initial consultation in Augusta. It wasn’t what I needed, didn’t feel it. So, I went home and I began to pray. ‘Lord, where should I go? What should I do?’ And God spoke to me and said, ‘Come to Duke.’ So I was led here by divine intervention. And I’m happy that I did.
When I came here for the initial consultation, my family and I met with Dr. Kevin Naresh Shah, and I asked him, ‘How you gonna operate on me with them little hands?’ And he said, ‘I’m the damn best you got.’ Getting diagnosed with pancreatic cancer, of course, was a death sentence. But he told me he could do the laparoscopic Whipple and we did that for 12 hours and then I had to do massive chemotherapy.
That’s when I met Dr. John Howard Strickler. He had just gotten back from France from a pancreatic cancer forum. He said, ‘This (inaudible) is the greatest and you are the first patient,’ but he reassured me that I’ll be okay. He said, ‘Your attitude is great. Your faith is great. Your fitness is good. And we will be with you every step of the way.’ So, I had hope and encouragement. And don’t forget what he told me. Dr. Strickler told me he was gonna throw the papa-bear treatment at me. So we went through that for about a year. Then after that, I came back to Duke for radiation and oral chemo under Dr. Manisha Palta. So, she and her team were also great.
It has been a great, wonderful, remarkable experience for me at Duke. I tell everyone, everywhere I go, ‘If you want to live, you need to come to Duke.’ Let me say that again. ‘If you want to live, you need to come to Duke. It will never give up on you.’ And my hope, my faith, and my resilience has never been stronger.
I have a good friend now who has retinitis pigmentosa. I told him to come to Duke and now he’s here in the research program for retinitis pigmentosa. Every chance I get, I’m telling my story, because I’m a miracle to survive pancreatic cancer.
But I also tell the story of Duke being my support system. Everyone, I told everyone, that from the time I park my car until I get to the labs, to the CT scan, this has been a wonderful, rewarding experience for me, and I hope to finish this journey with Duke that I started. It’s been remarkable. It’s awesome. And this just this gives me resilience and the tenacity to want to fight and want to win. Because when I come back to Duke, I want them to see that we are doing well because of Duke and you all. That’s why I’m here. Thank you.”
Pancreatic cancer survivors John Sanders and Tom Shankle engage in their best tomfoolery, ensuring they get a laugh or two out of Sheridan van Wagenberg, Caring House executive director. “Caring House counts on guest lifting one another up," she says. "Not everyone comes her ready to take on the world. At Caring House, if a guest is down there’s always another guest ready to lift that person up.” (photo by Karen Butler)
DCI Executive Director Michael Kastan, MD, PhD, presents lymphoma survivor Ovester Grays with a gift basket of thanks from DCI. (photo by Nolan Miller)
“Thank you Ovester, Elle, John… Don’t we have the most inspiring patients ever?” said Kastan, in closing. “I’m truly grateful for these amazing patients and I appreciate their inspiring stories. And I truly appreciate Dean Klotman and Dr. Albanese. The future of cancer care at Duke Health is bright. Thank you for celebrating this landmark anniversary with us as we advance health together.”
Post-program festivities included a reprise by the Duke Marching Band, giveaways of DCI 50th-branded lanterns and drawstring bags, boxed lunches, and an opportunity to sign the DCI 50th banner.
The sounds of talented saxophonist and flutist Tim Smith wafted through the chatter of colleagues catching up — some of them reuniting for the first time after a two-year Covid-19 lockdown.
Tim Smith is an Artist in Residence with Duke Arts and Health. He has previously worked on Sesame Street and was a member of Squirrel Nut Zippers swing and jazz band. (photo by Drawbridge Media)
Event planners Tina Piccirilli (program manager, Facilities, and a 30-year veteran of Duke), retired DCI nurse and administrator Jana Wagenseller, RN, Rob Odom and Shelby Boyd (Duke Health Marketing) together with Kristy Sartin, LRT/CTRS (program manager, Duke Supportive Care and Survivorship Center, cancer survivor, and 16-year veteran of DCI) and a small group of volunteers, made sure the day’s events went as smoothly as planned.
A Duke Health communications team was also on hand to record the milestone celebration with photos and videotaped interviews, assuring that it would be documented for future generations.
The darkening skies with intermittent breakthroughs of strong sunlight seemed to mirror the current cancer climate — sadness for those lost and the sober recognition that there’s more work left to do toward cures, but also gratitude for a much better today with great hope for an even brighter tomorrow.
Watch the DCI 50th Celebration Highlight Reel (below)
TED ALYEA, MD: Chief Medical Officer, DCI, and hematologic oncologist, Adult Blood and Marrow Transplant Program
“I joined DCI about two years ago and it’s been wonderful to be back. I found a great group of people who I knew were here. They've all been very welcoming. They're all committed to a common goal of helping people and their families fight cancer, to live better and more full lives. So, it's really wonderful to be part of that team.” (Alyea received his MD from Duke in 1989. His grandfather — Edwin P. Alyea, a surgical urologist — was one of the original group that founded the Duke University Medical Center. The senior Alyea was the first member of the Urology faculty — teaching from 1930 to 1969 — and for much of his career served as chief of that department)
Q: Do you think DCI is going to be here for another 50 years — that the cancer fight will take that long?
“Nothing would make me happier than for us (the cancer field) to go out of business, but we have a lot of work to do in between for that. And, you know, I think if you're asking me what the future holds, I think a lot of it's going to be in advancing prevention and being able to manage cancers, as we learn more and more. In some cases we’ll be successful in preventing them and in other cases we'll be successful in preventing them from causing problems — managing them over the long term."
“There are many disease settings where we see that's indeed the case — where many of these targeted therapies are being used as a way to turn cancer into a chronic illness. I think that therapies will improve. We'll see some escape mechanisms that develop and we will learn from different types of settings. But, you know, I view this as a challenge in each of the cancer disease areas.”
ROBIN FAMIGLIETTI, PHD, MBA, FACHE
Associate Dean and Chief Administrator, DCI, Associate VP Oncology Services, DUHS
Q: Where do you think DCI will be in 50 years? Will DCI and the field be done tackling cancer?
“You know, I absolutely think we're just going to be making amazing strides when you look at what we're doing with personalized targeted cancer treatment. You know, what I say all the time is where I think DCI is going to be is not only giving the right treatment to the right patient at the right time, but we're going to do so in a compassionate and supportive manner, which is what really makes us unique — that we treat the patient, we take care of their families, and their caregivers. I think we're just going to be doing that tenfold times better because we're going to learn as we go.” Famiglietti joined DCI in March 2019.
KEVIN OEFFINGER, MD, FASCO
Director, Duke Center for Onco-Primary Care, and Director, Duke Supportive Care and Survivorship Center
"The story from the young woman with metastatic colorectal cancer is apropos. The National Cancer Institute (NCI) is very interested in the healthcare needs of individuals with metastatic cancer or chronic cancer. We will be submitting an application for a grant to the NCI to understand the needs of individuals living with a chronic cancer and focusing on financial toxicity and promoting adherence to medications. We have a multidisciplinary team working on this — our CLL (chronic lymphocytic lymphoma) team and our prostate cancer group — looking at what we can do to improve communication and improve long-term outcomes. It reflects what's going on in the world. So when we hear somebody say, 'I had metastatic colorectal cancer six years ago,' that's a reality. We're seeing that on an everyday basis. And the question is, what are their needs long-term because we've never really studied it."
"People have often thought of 'survivor' as somebody that finished curative therapy. But we certainly think of our patients with either chronic cancer or with metastatic disease that are treated on an ad hoc basis (as survivors)."
"We have several studies in progress — a large team, a lot of clinical efforts — and we're training and educating our fellows, our residents, our medical and nursing students, our psychologists, etc. It's an exciting time. In one of our studies, we're working with two of our Duke Cancer Network hospitals down on Laurinburg and Lumberton, enrolling patients with newly diagnosed solid tumors and trying to make sure that their cardiovascular medications are managed while they're going through their therapy — really getting their PCP engaged and reminding the patient that we can cure the cancer, but we can lose the fight with a heart attack. We want to prevent that."
"It's a great time for clinical care, research, and training in this area. And policy."
Oeffinger joined DCI in April 2017.
ANN-MARIE PETERS, RN
Senior Clinical Research Nurse Coordinator, Thoracic Oncology
“I don't have any thoughts as to what the next 50 is going to look like, but what I do know, what I want, is for people to live with cancer longer. I have seen that over the past 10 years and I'm hoping that some of those people who have survived this long can continue to live longer. We might not have a cure, but we really want this to be just a chronic disease that is very manageable. That’s my hope. That’s the biggest bright spot — good quality of life and longer life."
TASHA JOHNSON
Pediatric Phlebotomist, Duke Children's Health Center
Q: Have you seen improvements in the last 10 years as far as treatments and survival?
“Somewhat, yeah. We see the same kids young growing up and getting better. A lot of them come back (for visits) due to the illness that they may have. And we see them on both sides. We see them on the clinic side at the CHC (Duke Children’s Health Center) and then we also see them over in inpatient. I have to stick the angels, the children with needles. I love it though. I love what I do.”
Q: Do you think we’re going to still be here fighting cancer in 50 years?
“Yes, I do. I think we are working hard towards it (getting rid of cancer), but I don't know. I think we might still be here.”
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.”