DCI gynecological cancer physicians and researchers provide comprehensive cancer treatment and conduct research that is bringing us closer to understanding, detecting, treating, and improving outcomes for people with gynecological cancers.
Visit DukeHealth.org for more information about gynecologic cancer treatment.
Our gynecological cancer team includes gynecologic oncologists, radiation oncologists and research collaborators. We offer patients the latest approaches in surgery (including laparoscopic and robotic), chemotherapy, biological therapies, radiation, and brachytherapy for the treatment of ovarian, cervical, uterine, vaginal, and vulvar cancers. We are also leaders in the diagnosis and treatment of hereditary gynecologic cancers. Learn more about some of the major research programs ongoing in the Gynecological Cancer Program by clicking on the Research tab.
We have had leadership roles in a wide range of cooperative group therapeutic clinical trials that have defined the standard of care for surgery, radiation, and systemic therapies in gynecologic malignancies. Recent discoveries in cancer biology have led to the development of new biomarker-directed therapeutic approaches for gynecologic cancers. This most notably includes the use of PARP inhibitors in ovarian cancer and immune checkpoint inhibitors in uterine cancer, but other targetable alterations also exist.
In 2019, Dr. Angeles Secord founded a consortium of peer academic institutions to better define the use of targeted biological agents in metastatic endometrial cancer. The centralized database for the consortium, which is housed at Duke, now includes over 2,000 patients.
Ovarian cancer is the most lethal gynecologic malignancy due late stage presentation as a result of a lack of effective screening and prevention approaches. The International Ovarian Cancer Association Consortium (OCAC) was formed in 2005 to better understand the genetic and behavioral factors that affect ovarian cancer risk. OCAC now includes over 100,000 research subjects from many case-control studies. Dr. Andrew Berchuck has served as the head of the OCAC steering committee since the inception of the group. About 40 common low penetrance genetic risk variants have been identified through genome-wide association studies, as have epidemiological risk factors. This provides the basis for improved risk stratification that could aid the implementation of personalized risk-reducing strategies including prophylactic surgery, screening, and chemoprevention.
Our group was awarded an NCI cancer, intervention, and surveillance modeling network (CISNET) grant in 2022 to work on mathematical models of uterine cancer to help inform strategies for prevention and improved outcomes for uterine cancer. We are working on tools to help address the growing uterine cancer incidence and mortality in the US. There are striking disparities in both incidence and mortality between black and white women, both nationally, and in North Carolina. Dr. Laura Havrilesky is the principal investigator for CISNET and this work also involves Evan Myers MD, MPH. Dr. Havrilesky is also involved in a wide range of quality improvement and health services research projects. This includes studies that assess the impact of patient preferences on clinical decision-making in ovarian cancer.
Drs. Laura Havrilesky and Brittany Davidson have collaborated to address issues surrounding the end-of-life decisions of women with ovarian cancer. This has focused on communication skills that facilitate difficult conversations. Earlier goals of care conversations with patients who have limited life expectancy facilitate earlier hospice enrollment and better quality of life while reducing hospitalizations and futile treatment. Dr. Davidson also conducts research related to patient adherence with oral anticancer medicines and optimization of oral pain medication use after surgery.
Cervical cancer is a highly preventable disease in the developed world due to the wide availability of cervical screening and HPV vaccination. In developing countries lack of access to these preventive approaches remains an unfortunate reality. Dr. Megan Huchko and Dr. Nimmi Ramanujam have led efforts, including in Peru and Kenya, to address barriers to early detection and screening with education, cultural awareness, and clinical tools - such as HPV self-sampling, pocket colposcopy, thermal ablation, and decision-making algorithms to community-based clinics. This focus on technology and implementation strategies has the potential to allow more accurate and lower-cost cervical cancer screening to reach millions of women living in low- and middle-income settings. Dr. Davidson serves on the steering committee for the American Cancer Society Round Table on Cervical Cancer, a group that aims to eliminate cervical cancer diagnoses by increasing access to guideline-based prevention, screening, and treatment techniques.
Dr. Hayley Moss Appointed Founding Director of National VA Program on Women's Cancers
Dr. Haley Moss, MD, MBA is involved in work seeking to understand challenges related to the implementation of gynecologic oncology care, including screening, cost of care, and the impact of the Affordable Care Act on access to cancer services. In 2021, she was appointed founding director of a national VA (U.S. Department of Veterans Affairs) program in women’s cancers.
Tomi Akinyemiju, Ph.D. is an epidemiologist in the Duke Population Health group whose work focuses on racial disparities in women’s cancer care. She is performing a prospective cohort study of 1,600 Black, Hispanic, and White ovarian cancer patients in the US characterizing multiple healthcare access domains and how they individually and synergistically influence receipt of guideline-adherent primary treatment, supportive care, and survival. These studies are intended to provide novel, empirical, and generalizable insights that can help identify and prioritize specific modifiable factors that can be targeted to reduce cancer disparities and improve care for all patients.
Finally, Drs. Emma Rossi and Leah McNally are involved in a wide range of research and educational programs related to the surgical management of gynecologic cancers. This work focuses mainly on the use of minimally invasive laparoscopic and robotic approaches that lead to better patient outcomes.
This spring, the "Andrew Berchuck, MD, Gynecologic Oncology Endowed Lectureship" was established in celebration of Dr. Berchuck's "remarkable legacy to the subspecialty of gynecologic oncology and to training the next generation of physicians dedicated to research, education, and patient care."
Andrew Berchuck, MD, the James M. Ingram Distinguished Professor of Gynecologic Oncology, is the third and current chief of the Division of Gynecologic Oncology (2005 to present) in the Duke Department of Obstetrics and Gynecology. An accomplished gynecologic oncologist and researcher, he also directs the Duke Cancer Institute Gynecologic Cancer Disease Group, and is co-director, with Jennifer Plichta, MD, MS, of Cancer Genetics at DCI.
Berchuck joined the Duke Comprehensive Cancer Center (now DCI) in 1987. Since day one he’s led a research program focused on the molecular-genetic alterations involved in the malignant transformation of the ovarian and endometrial epithelium. He maintains a clinical practice in surgical and medication management of individuals with ovarian, endometrial, and lower genital tract cancers.
Along the way, he's had the privilege to train about 40 fellows and some 250 residents. And while Berchuck has been at Duke long enough to witness some medical students become residents, then fellows, and eventually partners, the focus of the endowment, he said, is to re-establish and maintain connections with former Division fellows who are no longer at Duke and bring them back to learn about their work and how the training they received at Duke has served them in their careers through the annual oncology lectureship and possibly other events.
It was in that vein that the Division's second chief Daniel Clarke-Pearson, MD, a Duke resident and fellow in the 1970s who went on to lead the Division of Gynecologic Oncology from 1987 to 2005 — was invited to deliver the inaugural "Andrew Berchuck, MD, Gynecologic Oncology Endowed Lecture" on May 31.
Said Ob/Gyn Department Chair Matthew Barber, MD, before introducing the speaker that morning, "As I was thinking about this endowment and Andy, the one word that kept coming to mind was impact. And he has had just an incredible impact on this institution, on the Division of Gynecologic Oncology, on the Duke Cancer Institute, on the field of gynecologic oncology, and on the thousands of patients that he's had the opportunity to care for, as well as (his impact on) many medical students, residents, and fellows, and he's done it in so many ways — as a compassionate caregiver, as an extremely skilled surgeon, as an innovator, as a scientist, as a mentor, as a teacher, as a leader. And, in fact, I would say that Dr. Berchuck really is the archetype of the Triple Threat."
Duke Cancer Institute gynecologic oncologist and Professor of Obstetrics and Gynecology Angeles Alvarez Secord, MD, MHSc, was officially installed as president of the Society of Gynecologic Oncology at the Society's Annual Meeting, held March 25-28, 2023.
“It is my privilege and honor to serve as the 55th president of SGO,” Secord said at the meeting. “The theme for our year is ‘The Power of Shared Purpose: Transforming Gynecologic Cancer Care.’”
Secord, who serves as associate director of clinical research in DCI's Gynecologic Cancer Disease Group, has been a member of the faculty since 2001. She's been member of DCI since 1994 when she first joined Duke as an OB-GYN resident after earning her MD at the University of Washington. From 1998 to 2001, she was a DCI GynOnc fellow. She was named a full professor in 2013.
Secord's research is centered on novel therapeutics, biomarkers, and clinical trial development for ovarian and endometrial cancer. A national leader in the field, her efforts contributed to the approval in 2017 of Niraparib, a PARP inhibitor, to treat ovarian cancer.
Secord already had a national profile prior to her election as SGO president. She has been an active member of SGO since 2001; serving initially on the SGO Fellow’s Task Force and later as chair of the Candidate’s Task Force. She was inspired to serve SGO further during her role as an ex-officio member on the SGO Council from 2003 to 2005 and, according to an article by SGO introducing her as its new president, "credits that experience for opening the door to future leadership possibilities."
Secord has participated on several SGO and Foundation for Women’s Cancer committees, task force initiatives and program committees. She serves as co-chair of Education and Mentoring at the GOG (Gynecologic Oncology Group) Foundation; chair of the Scholar Committee at the American Association of Obstetricians and Gynecologists Foundation; and vice chair of the New Investigator Committee at NRG Oncology. Secord is a fellow of the American College of Obstetricians and Gynecologists and an active member of American Society of Clinical Oncology, the American Gynecological & Obstetrical Society, and the International Gynecologic Cancer Society.
Duke Cancer Institute has named five DCI faculty to new leadership roles.
Andrew Berchuck, MD, and Jennifer Plichta, MD, MS, have been named co-directors of Cancer Genetics at DCI.
They replace breast surgical oncologist Carolyn Menendez, MD, who has a new role as director of Clinical Cancer Genetics, National Oncology, Precision Oncology, and TeleOncology Programs, U.S. Department of Veterans Affairs (based in Durham).
Berchuck, a gynecologic oncologist, is chief of the Division of Gynecologic Oncology. He is the James M. Ingram Distinguished Professor of Gynecologic Oncology and a professor in the Department of Obstetrics and Gynecology.
Plichta, a breast surgical oncologist, is director of the Duke Breast Risk Assessment Clinic. She is an associate professor in the Departments of Surgery and Population Health Sciences and is a BIRCWH scholar.
The aims of the Clinical Cancer Genetics Program include advancing cancer genetics research, establishing a carriers clinic and expanding point-of-care across all disease sites.
Neuro-Oncology Research Program
Gerald Grant, MD, has been named co-leader of the NCI-designated DCI Neuro-Oncology Research Program. Grant replaces David Ashley, PhD, FRACP, MBBS (Hons), who has decided to step down from this role. Grant joins Kyle Walsh, MD, current co-leader of the program.
Grant, a professor in the Department of Neurosurgery, is chair of the Department of Neurosurgery and a pediatric neurosurgeon.
Radiation Oncology and Imaging Research Program
Chuan-Yuan Li, DSc, has been named co-leader of the NCI-designated DCI Radiation Oncology and Imaging Research Program.
Li joins Nimmi Ramanujam, PhD, and Manisha Palta, MD, current co-leaders of the program. Li replaces David Kirsch, MD, PhD, who was recently named director of the Radiation Medicine Program at the Princess Margaret Cancer Centre in Toronto, Canada.
Li, a professor in the Departments of Dermatology and Pharmacology and Cancer Biology, is the vice chair for research in the Department of Dermatology and an affiliate member of the Duke Regeneration Center, Regeneration Next Initiative. Li has previously served as co-chair of the DCI’s Scientific Review Committee.
DCI Scientific Review Committee
Kris Wood, PhD, has been appointed co-chair of the DCI Scientific Review Committee, replacing Chuan-Yuan Li, DSc, who's been named co-program leader for Radiation Oncology and Imaging.
Wood, an associate professor in the Departments of Pharmacology & Cancer Biology and Cell Biology, is a member of the DCI Precision Cancer Medicine and Investigational Therapeutics Research Program. He is also core faculty with Duke Innovation & Entrepreneurship.
Duke Cancer Institute Blog
Tomi Akinyemiju, PhD, social and molecular cancer epidemiologist and associate director, Community Outreach, Engagement and Equity (COEE) at DCI, and Rebecca Previs, MD, adjunct gynecologic oncology faculty.
Last month (October 24, 2022), three Duke Cancer Institute facultyin the Department of OB-GYN, Division of Gynecologic Oncology —Brittany Davidson, MD;Haley Moss, MD, MBA; andAngeles Alvarez Secord, MD, MSc—andaDCI faculty member in the Department of Medicine, Division ofPopulation Health Sciences (Arif Kamal, MD, MBA, MHS)participated in national-level events under the auspices of theWhite House Cancer Moonshot Initiative.First launched in 2016 by the Obama administration and led by then-Vice President Joe Biden to“accelerate scientific discovery in cancer, foster greater collaboration, and improve the sharing of cancer data,” theCancer Moonshotwas reignited in February 2022 byPresident Joe Biden and First Lady Jill Biden,Ed.D.The new goals are to “reduce the cancer death rate by half within 25 years and to improve the lives of people with cancer and cancer survivors.”(The Cancer Moonshot was not active during the Trump administration.)In October, the focus was on breast and gynecologic cancers.
According to the National Cancer Institute, nearly 20,000 women in the U.S. will be diagnosed with ovarian cancer — which encompasses the ovaries, fallopian tubes, and the primary peritoneum — and nearly 13,000 are expected to die from the disease in 2022.
Despite clinical guidelines advising against intensive or invasive end-of-life care, more than half of patients with terminal ovarian cancer will receive a least one aggressive intervention near the end of life — such as undergoing chemotherapy treatment, being admitted to the intensive care unit, or being admitted to hospice, at such times that, research shows, these interventions wouldn't help prolong their life and would actually worsen their quality of life.
According to Duke Cancer Institute gynecologic oncology faculty Brittany Davidson, MD, and Laura Havrilesky, MD, as well as University of Colorado Anschutz Medical Campus faculty Carolyn Lefkowitz, MD, there is often a lack of understanding or absence of communication about palliative care options and reducing aggressive end-of-life care.
“What we should be striving for near the end of life is goal-concordant care, focused on the delivery of medical care in line with an individual patient’s values and goals for treatment and respecting any limitations delineated by the patient. For the majority of patients, aggressive end-of-life care is not
what they want,” they wrote in an editorial for the March 2022 issue of JCO Oncology Practice (originally published online on Nov. 8, 2021).
The editorial was published as a companion piece to a JCO Oncology Practice article by the University of Michigan, Ann Arbor, MI, and Wayne State University researchers on the role of “physician influence” on aggressive end-of-life care in women dying from ovarian cancer.
Lead author of the editorial Brittany Davidson, MD, a DCI gynecologic oncologist, associate professor in the Department of OB-GYN, Division of Gynecologic Oncology, and the director of gynecologic oncology fellowships, shares how she and her colleagues at Duke are approaching goal planning, palliative care, and end-of-life care in the clinic in this Duke Cancer Institute/Duke Division of Gynecologic Oncology Q & A feature.
Duke Cancer Institute Blog
William Creasman, MD, considered one of the founding fathers of the subspecialty of gynecologic oncology, was hired by then-Department of Obstetrics & Gynecology chair Roy T. Parker, MD (now deceased), in 1970 as the first fellowship-trained gynecologic oncologist at Duke and was the founder of the department’s Division of Gynecologic Oncology in 1972. Creasman is currently a professor at the Medical University of South Carolina. (photo courtesy of Duke Medical Archives, circa the 1970s)
In 1972, William T. Creasman, MD, established the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology at Duke, becoming the division’s first chief. This coincided with Duke becoming an officially designated Comprehensive Cancer Center by the National Cancer Institute, then under the leadership of William Shingleton, MD. Four years before, Duke had already made its first big mark in the gynecologic oncology field.In 1968, Charles B. Hammond, MD, then a clinical associate, founded the Southeastern Regional Trophoblastic Disease Center at Duke, the first center of its kind in the region to combat gestational trophoblastic disease, the development of abnormal cells inside the uterus in the tissues surrounding the fertilized egg that can go on to form cancerous and benign tumors.Using what he learned at the National Institutes of Health, Duke gynecologists were able to offer patients chemotherapy treatment to prevent the malignant form of the disease from spreading.“Probably the thing I’m most proud of is, I was lucky enough to go to the National Institutes of Health in the mid-60s at a time when malignancy was being treated that grew from the placenta, or the afterbirth — a universally fatal disease,” noted Hammond, who passed away in February 2021, in a 2011 Duke Medicine (now Duke Health) video chronicling his career highlights. “Someone there had just made a discovery that showed it could be cured with drugs, and while I was there, we refined those drugs; expanded the cure rate to approach 100 percent. The fundamental idea of using drugs in that disease was a radical new one. It had been tried but really hadn’t been proven. And when I was there, we were able to try it on nearly 100 patients … and then expanded to the center here [at Duke]. It transformed a disease, one of the first diseases that was ever cured with chemotherapy. It was a very gratifying time. We didn’t cure everyone, particularly in those early years, and some patients, unfortunately, had complications of the treatment… that’s how we learned.”The commitment of the Division and Duke Cancer Institute to research and innovation in gynecologic cancers continued throughout the 20th century and entered a new era of discovery in the 21st century.From individualized treatment, including targeted therapies and immunotherapy; to lifesaving surgical procedures and clinical trial opportunities across disciplines for patients who otherwise would not have treatment options available; to the burgeoning field of onco-fertility(fertility preservation options for cancer patients); treating gynecological cancers has come a long way.Importantly, as a multitude of treatment options have become available, there’s been a greater focus on quality, safety, affordability, and improved provider-patient communication around treatment goals and quality of life.And gynecologic oncology faculty have also made global inroads in gynecological care and research — establishing partnerships in more than 10 countries across four continents.
Duke Cancer Institute Blog
Duke Cancer Institute gynecologic oncologist Haley Moss, MD, MBA, has assumed the role of Director of the U.S. Department of Veterans Affairs Breast & GynOnc Cancers Program.
Duke Cancer Institute memberHaley Moss, MD, MBA,recently joined the U.S. Department of Veterans Affairs' National Oncology Program Office as director of theBreast and Gynecologic Cancer System of Excellence, which aims to advance and expand women Veterans' access to teleoncology and potentially lifesaving clinical trials and treatments."In the past two decades, there has been an unprecedented growth of women Veterans seeking medical care through the Veterans Health Administration. In response to the ever-growing population of women Veterans, the National Oncology Program Office through the VHA has developed the Breast and Gynecologic Cancer System of Excellence," said Moss. "We will be establishing partnerships with universities and National Cancer Institute-designated cancer centers to promote breast and gynecologic cancer research and increase opportunities for these patients to participate on clinical trials. We will provide care coordination services to patients who may need to go between the VA and other health systems as they navigate their cancer care."Moss joined DCI asan assistant professorin the Department ofObstetrics and Gynecology in 2019 following a three-year fellowship with that department. Moss' research "has focused on the interface of women’s health and policies to improve the value of cancer care."She is also apracticing gynecologic oncologistwho sees patients in clinic at Duke Cancer Center Durham and Duke Women's Cancer Care Raleigh as well as at Duke University Hospital and Duke Raleigh Hospital.With the new role, Moss retainsher faculty and clinical positions at Duke.
The February installment of the DCI Office of Health Equity's "Conversations with Our Community" — How Studying Genes Can Lead to More Personalized Cancer Care (recorded on 2.24.21) — featured co-director of the Patierno/George/ Freedman Lab for Cancer Research Jennifer Freedman, PhD, and postdocs in the lab Tyler Allen, PhD, and Sean Piwarski, PhD — all of whom shared their research into identifying genes in cells that drive cancer disparities and developing treatments that block those genes. The community forum was moderated by Angelo Moore, PhD, RN, who leads the Office of Health Equity (OHE).
“We welcome any input we can get from the community. We really want to work with the community side by side to address the questions we are trying to address and do all the work that we do," Freedman said, leading off her presentation. “We have a lot of evidence in cancer and other diseases that it really needs to be personalized, that members of different population groups get cancer at very different rates.They have cancers that vary in risk, in aggressiveness and in response to treatment.”
Freedman referenced some of these striking disparities:
African American women are nearly twice as likely as white women to be diagnosed with triple-negative breast cancer and are much more likely than white women to die from breast cancer.
The highest rates of kidney cancer cases in thee U.S. occur among American Indians/Alaska Natives.
Rates of liver cancer are higher among American Indians/Alaska Natives and Asian and Pacific Islanders than other racial/ethnic groups
African American men are more than twice as likely as white men to die from prostate cancer.
Women in rural areas are twice as likely to die from cervical cancer as women in more urban areas.
African Americans are twice as likely as Whites to be diagnosed with and die from multiple myeloma.
White people are much more likely to get glioblastoma and to die from it than members of other racial and ethnic groups.
While this particular set of talks focused on genetic drivers of cancer, Freedman emphasized that there are other factors, including society-level factors such as racism and discrimination; neighborhood-level factors such as diet, lifestyle, the environment, pollution; and institutional-level factors such as access to getting care.
"All of these factors — genetics, what’s happening at the society level, what’s happening in our neighborhoods and what’s happening with our access to institutions all influence our risk of getting cancer, how bad our cancer is, how it progresses and if we have cancer how we respond to treatment," said Freedman. "We really need to think about these factors together, how they interact, when we’re doing the work we are doing."
Allen described his work in the lab studying cancer metastasis and how it’s different in different racial or ethnic groups and how the lab is using CRISPR gene editing to control RNA splicing. Splicing dysfunction underlies many conditions and diseases, including cancer.
"The information gained from studying these genes allows us to then develop drugs to target the identified changes in genes and RNA splicing," Allen explained. "These therapies can be tested in the lab and clinical trials and, if safe and effective, can then be used to treat cancer patients."
Piwarski zeroed in on prostate cancer disparities among racial and ethnic groups, including incidence rates and death rates. He also spoke about the group’s ABI-Race clinical trial in which they trialed a particular treatment for advanced prostate cancer in African American patients and in White patients — both equally represented — and what they learned about the differences in response to treatment. (Data presented at the 2018 ASCO Annual Meeting suggested that African-American patients responded better to the treatment, per study PI Dan George, MD, who co-directs the Patierno/George/Freedman Lab.)
Research led by Duke Cancer Institute’s Jen-Tsan Ashley Chi, MD, PhD could have implications for the successful treatment of certain types of ovarian, breast and kidney cancerThe American Association for Cancer Research (AACR) has named Jen-Tsan Ashley Chi, MD, PhD, as co-winner of the Molecular Cancer Research Michael B. Kastan Award for Research Excellence on behalf of his all-Duke research team for their paper — A TAZ-ANGPTL4-NOX2 Axis Regulates Ferroptotic Cell Death and Chemoresistance in Epithelial Ovarian Cancer. Chi is co-director of the Cancer Biology Research Program at Duke Cancer Institute and directs his own lab within the Duke Center for Genomic and Computational Biology that's focused on the adaptation and response of cancer cells to various stresses in the tumor micro-environment. He's an associate professor in the Department of Molecular Genetics and Microbiology, an associate professor in the Department of Pharmacology & Cancer Biology, an assistant professor in the Department of Medicine, and an assistant professor in the Department of Radiation Oncology.The Michael B. Kastan Award for Research Excellence is formally bestowed on the first or corresponding author of an article in Molecular Cancer Research (the flagship AACR journal for fundamental cancer research discoveries) that's had a significant impact on the fields represented by the journal, but all co-authors are named as recipients of the award in recognition of the importance of team science. The MCR editor-in-chief and two additional editors for the journal select the award recipient (s) — prioritizing those articles that “have the potential to shift paradigms, inspire translational activity, and raise awareness of new scientific areas” and which are “representative of the journal in terms of originality/ novelty, scientific/clinical merit, and/or impact/significance."Chi’s co-authors on the winning paper, which was published in the January 2020 issue of MCR, include: Wen-Hsuan Yang, PhD (first author of the paper, then a PhD student in the Chi Lab; Zhiqing Huang, MD, PhD (assistant professor in Obstetrics and Gynecology and a DCI member); Jianli Wu, BS (lab research analyst 1 in the Chi Lab); Chien-Kuang C. Ding, MD, PhD (with Duke at time of publication; now a pathology resident with the University of California, San Francisco); and Susan K. Murphy, PhD (associate professor in Obstetrics and Gynecology and a DCI member).Given yearly since 2019, the award was established by AACR in 2018 in honor of Michael B. Kastan, MD, PhD, the journal's founding editor-in-chief (in 2002). (Kastan, who has served as executive director of Duke Cancer Institute since 2011, plays no role in the selection process.)AACR created the award in recognition of Kastan’s “vision and dedication to publishing exceptional scientific findings” that facilitated the field’s understanding of factors that influence cancer development and progression at the molecular level.“It has been humbling that the AACR has honored me in this way for my efforts with this journal over the years," said Kastan, an experienced investigator recognized for his discoveries in molecular biology, signal transduction and DNA damage and repair, "but I have to admit that having the award go to a DCI member this year is truly special. Dr. Chi is an exceptional scientist and I am so proud to have him as a colleague.”“I feel very honored to receive this prestigious award named for Dr. Kastan and I appreciate the excellent work of my lab members, especially first author Wen-Hsuan Yang and Susan Murphy,” said Chi.A Novel ApproachOvarian cancer is the deadliest gynecologic cancer. Despite recent advances in targeted and chemotherapy treatments, ovarian cancer cells like other cancer cells eventually develop a resistance to these treatments. Clinical outcomes remain poor, necessitating novel therapeutic approaches.Chi and his team have found, through nutrient drop-out screening/testing of 15 amino acids on a panel of nine clear cell and serous ovarian cancer cells, that most ovarian cancer cells need and are addicted to cystine — an amino acid (protein building block) that’s found in most high-protein foods, including chicken, turkey, yogurt, cheese, eggs, sunflower seeds and legumes.Depriving ovarian cancer cells of cystine, they discovered, leads to ferroptosis — a form of iron-dependent regulated cell death. Cystine deprivation starts this process of necrosis by generating a pore in the cell membrane that allows water to enter the cell, resulting in its death.Conventional chemotherapy, meanwhile, triggers a different form of cell death called apoptosis. Because these two methods use different mechanisms to kill cancer cells, cystine deprivation may be able to kill tumors that have proven resistant to some chemotherapy treatments.“Ovarian cancer cells have a special need for outside nutrients that may allow us to pre-emptively reduce or eradicate the recurrent disease. Just as we require food (sugars or proteins) and oxygen to live, our cells also rely on outside nutrients they must obtain from their environment for their survival,” Chi explained. “Compared to normal cells, cancer cells often have increased and different demands for nutrients from the surrounding environment, including the extracellular amino acid cystine, for survival. The removal of cystine rapidly triggers a special kind of cell death called “ferroptosis” that even resistant cells are still sensitive to. Most amino acids, when you take them out, the cancer cells just stop growing, but they can still live. Cystine they just can’t deal without, and they die very extensively.”In addition, the research team found that the cell density makes a difference as to how sensitive the tumor cells are to cystine deprivation. While tumor cells grown far apart were very sensitive to cystine-deprived death, the same tumors became much less sensitive when grown crowded together. This discovery led them to the conclusion that a cell density sensor, TAZ, actually promotes the ferroptosis of the ovarian cancer cell lines. Since TAZ is an important protein regulating tumor growth and metastasis, their results suggest that ferroptosis may be particularly effective in TAZ-activated tumors.This research — reported out in the team's award-winning MCR paper — was partially funded, noted Chi, by a previous DCI pilot grant award to him and Murphy. The work will be further supported by a U.S. Department of Defense Ovarian Cancer Research Program grant to determine the therapeutic potential of using ferroptosis to fight chemotherapy-resistant ovarian cancer tumors. The team will attempt to remove cystine in mice (from those with ovarian cancer and also from those with renal cancer) using a novel form of recombinant cyst(e)inase — a human-engineered enzyme that acts on TAZ-activated tumors to trigger this ferroptosis.Recombinant cyst(e)inase is currently being developed by a drug company for clinical trials in various other (non-cancer) diseases.“We believe that triggering ferroptosis in cancer cells may overcome resistance to chemotherapy in ovarian and other TAZ-activated cancers as novel treatments,” said Chi, who’s spent the past 10 or 11 years investigating and publishing on the nutrient addictions of cancer cells in breast, ovarian and kidney cancers. “We have also found cystine addiction in triple-negative breast cancer cells and in renal (kidney) cancer cells that have lost the VHL tumor suppressor genes.”Chi added that treatment with cyst(e)inase could be further enhanced by adding immunotherapy or radiation to the treatment mix."Dr. Chi is an exceptionally creative scientist," said Steven Patierno, PhD, an internationally recognized expert in cancer control, cancer causation and molecular carcinogenesis who serves as deputy director of DCI. "He and his team are at the forefront of a rapidly evolving and critical aspect of translational cancer biology, at the intersection between tumor cell addiction to specific micronutrients and activation of novel pathways of cell death that may further sensitize tumor cells to targeted therapies. The pathways that this team are teasing out are themselves highly druggable and may be targets for future precision oncology approaches. Dr. Chi is highly deserving of this extraordinary award."Chi’s research team shares the 2021 Michael B. Kastan Award for Research Excellence with a research team led by David Maag, PhD, senior scientific director of AbbVie, Inc. in North Chicago, Illinois, for their paper — PARP1 Trapping by PARP Inhibitors Drives Cytotoxicity in Both Cancer Cells and Healthy Bone Marrow — published in the February 2019 issue of Molecular Cancer Research.The awardees and their winning papers are being highlighted this week at the 2021 (virtual) AACR Annual Meeting — April 10 to 15. (Week two will be held from May 17 to 21). The award is accompanied by a $500 cash prize and a certificate to each of the team leaders.Previous winners of the Michael B. Kastan Award for Research Excellence include Mohamed E. Salem with Levine Cancer Institute (2020) and Kenjiro Sawada with Osaka University Graduate School of Medicine, Suita, in Japan (2019).