Knight Cancer signal achievements of 2022

People at the Knight Cancer Institute accomplished a lot in 2022. Through innovative, collaborative research and education, the institute delivers cancer prevention, detection, and care — one person at a time. Here’s a look back at an array of achievements reflecting that mission.

 

Delivering discoveries

Detecting tumor responses before they become deadly:  In a step toward longer lasting treatments, Knight Cancer researchers have shown how it’s possible to track the evolution of a person’s disease quickly and closely enough to detect drug resistance mechanisms as they arise. Brett Johnson, Ph.D., first author of a paper describing the research, said the work was only possible through the combined efforts of an interdisciplinary team of clinicians and scientists brought together by the SMMART Program.

Blood test could reveal transition to cancer in people at risk: CEDAR scientists have devised an accurate and sensitive way to test blood to see if a pre-cancerous condition is escalating to outright cancer – potentially enabling treatment early in tumor development when cancer is more likely to be curable. Thuy Ngo, Ph.D., and colleagues reported the findings in NPJ Precision Oncology.

Rowan Callahan, Elias Spiliotopoulos, and Thuy Ngo, Ph.D, inside their lab at OHSU Knight Cancer Research Building on Friday, April 22, 2022. (OHSU/Christine Torres Hicks)

OHSU researchers ‘instrumental’ in study of new prostate cancer therapy:  The injected treatment combines a targeting compound with a radioactive isotope to irradiate and kill cancer cells. The Food and Drug Administration approved it for men with prostate cancer that has spread and become resistant to hormone therapy and chemotherapy. The OHSU Knight Cancer Institute was among the top sites for enrolling subjects in the clinical trial, giving early access to patients in Oregon. “This is a significant new treatment for patients with prostate cancer who previously had few options,” said Tom Beer, M.D.

To stop cancers, a new approach quickly finds novel drug combinations: Researchers at OHSU and Harvard are using an implanted microdevice to track tumors’ varying responses to a multitude of different drugs at the same time. “Although intended as a proof of concept that analyses of local nanodose drug responses can effectively guide systemic treatment strategies, we have already identified specific therapeutic combinations that warrant clinical consideration,” Joe Gray, Ph.D., and co-authors reported in Nature Biotechnology.

At age 68, Jerry Widawski was diagnosed with a rare and difficult-to-treat liver cancer. Surgical oncologist Skye Mayo, M.D., M.P.H., planned a series of operations including implanting a device to infuse chemotherapy drugs directly into the liver. More than two years after his last chemotherapy infusion, Widawski remained cancer-free. Now Mayo is leading a clinical trial to find out whether the treatment strategy can be extended to save more lives. Read the full story.

Sex hormone limits cancer immunotherapy success: OHSU researchers discovered how androgen hormones (most commonly testosterone in men) can limit the body’s response to cancer immunotherapy, a finding that may help make those therapies more consistently effective. The research by Amy Moran, Ph.D., and colleagues also sheds new light on what causes the immune system to function differently in men compared to women. A study in Nature co-authored by Moran found that androgens may partly explain why male sex is associated with worse cancer outcomes. The study found that women with metastatic melanoma have an improved response to BRAF/MEK-targeted therapy compared with men. In mouse models, drug inhibition of androgen receptor signaling improved responses to BRAF/MEK-targeted therapy in males and females. Testosterone administration was associated with a significantly impaired response to the therapy.

Preventing recurrence of cancer: About 70% of kidney cancers are diagnosed at a stage that can potentially be cured with surgery. But fatal cancers return after surgery in about a third of patients. Christopher Ryan, M.D., presented results showing that the drug everolimus has potential as an adjuvant treatment, particularly for patients at high risk of recurrence. People with kidney cancer who took the drug everolimus daily for up to one year after surgery were less likely to have a recurrence or die than those who did not take everolimus, although the results narrowly missed reaching statistical significance. “It has activity in this setting, and its potential utility warrants continued study,” Ryan said. He led the phase 3 clinical trial, called EVEREST, conducted by SWOG Cancer Research Network and supported by the National Cancer Institute.

Study reveals inherited risk of leukemia: More than 13% of adults with acute myeloid leukemia had inherited genes that likely predisposed them to the cancer, OHSU researchers found. The data support the need for routine screening for inherited predisposition genes in all patients with AML, said senior author Anupriya Agarwal, Ph.D. The team reached their findings by analyzing gene sequencing data on cancer tissue samples from 391 people with AML and manually classifying more than 1,500 sequence variations in 228 genes. It is the largest analysis of its kind of an AML patient population, the researchers said.

Potential new target for stopping a deadly leukemia: The discovery is the latest from the Knight Cancer Institute’s Beat AML platform for analyzing the cancer cell gene expression, drug sensitivities, and medical outcomes of more than 800 people with acute myeloid leukemia. “It’s giving us a better roadmap for understanding this disease,” said Jeff Tyner, Ph.D., co-author of a paper describing the new findings in Cancer Cell.

Better handle on breast cancer overdiagnosis: About 1 in 7 breast cancers discovered by mammography are overdiagnosed, according to a new study co-led by OHSU scientists. Overdiagnosis is when screening detects tumors that are non-threatening or too slow-growing to ever cause harm. “While our results confirm that breast cancer overdiagnosis is real, they also reassure that it is not as alarmingly frequent as the most prominent studies have suggested,” said co-author Ruth Etzioni, Ph.D., a distinguished scientist at CEDAR.

Recent childbirth is an independent risk factor for breast cancer progression: A study led by Pepper Schedin, Ph.D., found that the risks of metastasis and death were 50% higher among women with breast cancer diagnosed within five years of giving birth compared with those who had not given birth. These increased risks were independent of tumor stage or estrogen receptor status, the researchers found.

 

Serving the community

Helping all Oregonians contend with cancer: The Knight Cancer Institute created the Community Partnership Program to build sustainable collaborations across the state with organizations contending with local cancer needs. The program funded six new projects and renewed support for three others this year. “The Community Partnership Program has always been centered on the idea that communities know their needs best,” said Jackie Shannon, Ph.D., CPP co-director. In July, the program issued a special call for proposals to promote early detection. Those grants will help local groups develop and carry out plans to increase awareness and appropriate use of screening tests for cancer early detection.

The Community Hematology-Oncology team in Tualatin gathered for a ribbon cutting ceremony.

Building capacity for patient care. The Community Hematology-Oncology clinic in Tualatin nearly doubled its capacity this year, welcoming patients to the newly expanded unit on July 12. Located at Legacy Health’s Meridian Park Medical Center campus, it is part of the OHSU Knight-Legacy Health Cancer Collaborative. Another expansion is  underway at the CHO clinic in East Portland.

Establishing the benefits of exercise for cancer patients: An international panel including Kerri Winters-Stone, Ph.D., has published best practice recommendations on exercise for people with cancer that has spread to their bones. “This consensus guideline is the first of its kind and it addresses a very unique cancer population that can be left out of exercise guidelines due to safety concerns and lack of research,” Winters-Stone said. Amid the ongoing pandemic, a team led by Winters-Stone set up videoconferencing links to continue two large clinical trials of exercise for cancer survivors. In a new study, the researchers showed that tests used to track subjects’ physical functioning can be successfully adapted for remote administration.

Providing early access to multi-cancer blood tests: The Pathfinder 2 study is evaluating a blood test developed by GRAIL, Inc., that detects signs of more than 50 types of cancer with the goal of enabling earlier treatment. The Knight Cancer Institute was among the first centers involved in the first Pathfinder study. This year, the institute joined Pathfinder 2 and expanded access beyond the Portland area to people in five cities across the state in collaboration with local health systems.

Increasing equity in medicine and science: OHSU’s Summer Equity Research Internship earned national recognition with an award from INSIGHT Into Diversity magazine. College undergrads from communities underrepresented in science spend eight weeks doing research with OHSU mentors in the Center for Diversity & Inclusion’s program. Many Knight Cancer Institute scientists have stepped up as mentors. The Ted R. Lilley CURE Program is a research internship program supported by the Knight Cancer Institute that gives research experience to high school students who excel in science, but come from communities that are underrepresented in health and research professions.

A new mobile outreach van aims to meet community members around the state while improving the HPV vaccination rates in rural and frontier areas, bringing colorectal cancer screening education to communities and increasing diversity in clinical trials participation.

Top performer for CAR T therapies and stem cell transplants: OHSU ranks among the top 20 centers in the U.S. by number of stem cell transplants and Knight Cancer Institute physicians have been at the forefront of clinical trials for CAR T-cell therapies. This year, the Cell Therapy Laboratory opened a new cryopreservation facility to house stem cells and CAR T-cells for adults and children undergoing cell therapy at OHSU. The lab’s expansion will enable the program to grow and to serve more patients. The medical team on 14K enlisted a record-setting 333 potential new donors. “Our team takes care of people with life-threatening blood cancers and disorders. Their strength and courage are an inspiration to each of us,” said Kathie Phan, R.N., team lead for the donor registration drive with DKMS. “Our goal is to find a donor for everyone who needs a transplant so they have an opportunity for a second chance at life.”

 

Leading the way

Briefing the nation on research progress: As president of the American Association for Cancer Research, Lisa Coussens, Ph.D., unveiled the latest AACR Cancer Progress Report, which highlighted how federally funded basic research paves the way to life-saving advances in cancer prevention, detection, and treatment. The report makes the case for robust and predictable increases in federal funding to sustain momentum in the fight against cancer.

Lisa Coussens, Ph.D., (center) talks with constituents at the AACR Annual Meeting in April. (OHSU/Amanda Gibbs)

Advising the president of the United States: The Biden administration sought out Knight Cancer Institute Director Brian Druker, M.D., for perspective on the future of cancer care and research. His thoughts helped shape the direction of Biden’s Cancer Moonshot program.

Addressing gender inequity in oncology: Women in academic oncology continue to be underrepresented in leadership positions and as grant recipients and investigators in clinical trials. An article in JAMA Oncology co-authored by OHSU hem-onc fellows Malinda West, M.D., and Myung Sun Kim, M.D., presents a range of solutions to address the gender gap.

Advancing the early detection of cancer: Researchers from around the world gathered in Portland in October for the Early Detection of Cancer Conference organized by the OHSU Knight Cancer Institute, Cancer Research UK and the Canary Center at Stanford. Shelley Barton, Ph.D., co-director of CEDAR, served as scientific co-chair. Cancer early detection research is poised to transform patient survival, but significant hurdles stand in the way of translating new findings. A report in Science co-authored by Sadik Esener, Ph.D., and Lisa Coussens, Ph.D., details the challenges and charts a path to overcome them.

Maintaining excellence: The OHSU Knight Cancer Institute re-upped its accreditation with the Commission on Cancer, a quality program of the American College of Surgeons. To earn this status, a cancer program must meet 34 quality care standards, be evaluated every three years through a survey process, and maintain levels of excellence in the delivery of comprehensive patient-centered care. “Maintaining this accreditation is no easy feat, and I am thankful to my colleagues in the OHSU Cancer Committee for getting us across the finish line for another successful survey,” said Nima Nabavizadeh, M.D.

Inspiring philanthropy:  A $10 million gift from Norman and Linda Brenden to the OHSU Brenden-Colson Center for Pancreatic Care will bolster its efforts to help find better treatment strategies for patients with pancreatic disease. Brett Sheppard, M.D., co-director of the Brenden-Colson Center, said the gift will allow the center to continue to leverage its research expertise and closely collaborate with the OHSU Knight Cancer Institute and investigators around the world focused on finding pancreatic cancer earlier. The Kuni Foundation Foundation awarded $3.3 million for cancer research led by Amy Moran, Ph.D., Tanja Pejovic, M.D., Ph.D., Rajan Kulkarni, M.D., Ph.D., and Laura Heiser, Ph.D. UO football fans raised $66,300 for breast cancer research at OHSU by bidding on special-edition Duck football helmets.

Knight Cancer Institute employees gathered to thank the University of Oregon for supporting breast cancer research. (OHSU/Christine Torres Hicks)

 

Garnering honors

The National Cancer Institute awarded a National Research Service Award to Ashley Anderson, an M.D./Ph.D. candidate working in the laboratory of Melissa Wong, Ph.D. Anderson’s project aims to identify how hybrid cancer cells, defined by co-expression of immune and tumor characteristics, disseminate in patients with colorectal cancer so as to better understand tumor progression and the development of metastatic disease.

The American Cancer Society selected Ted Braun, M.D., Ph.D., for a Research Scholar Grant. The four-year, $792,000 award will support Braun’s project on therapeutic disruption of the MYC blood super-enhancer complex in acute myeloid leukemia.

Ana Dieguez in the OHSU Department of Radiation Medicine is one of two medical physics trainees in the U.S. awarded the 2022 Richard L. Morin Fellowship from the American College of Radiology. The fellowship provides hands-on experience with ACR and governance experience at the group’s annual meeting.

The Biomedical Engineering Society’s Cell and Molecular Bioengineering Conference selected Carolyn Schutt Ibsen, Ph.D., for its 2023 Rising Star Junior Faculty Award for her outstanding work in the field of cell and molecular bioengineering. She will be recognized at a gala dinner and provide a podium presentation in a special session at the annual conference in January.

Julia Maxson, Ph.D., who is working to understand how gene mutations turn normal blood cells into blood cancers, was selected for an LLS Scholar Award. She’ll receive $120,000 per year for five years.

Gordon Mills, M.D., Ph.D., was named Fellow of the AACR Academy, which cited his visionary efforts to advance precision medicine through genomics and systems biology, and his trailblazing the use of systems biology toward a personalized approach to breast cancer treatment.

CEDAR scientist Hisham Mohammed, Ph.D., was awarded a $600,000 grant from the V Foundation for Cancer Research for his proposal to develop a DNA methylation predictor for the early detection of acute myeloid leukemia.

Ellen Langer, Ph.D., was awarded a multi-year Research Scholar Grant of $792,000 from the American Cancer Society to research the biology underlying pancreatic tumor development to help develop more effective therapies.

Daniel Liefwalker, Ph.D., is one of 20 scholars selected by the National Cancer Institute for the first cohort of its Early Investigator Advancement Program, which aims to enhance professional skills, guide preparation of an R01 grant application, provide access to a mentoring and peer network, and grow a community of emerging independent investigators from diverse backgrounds.

Breanna Maniaci, a Ph.D. candidate in Julia Maxson’s lab, received the Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research from the National Heart, Lung and Blood Institute. Maniaci applied to support her thesis work on understanding oncogenic CSF3R signaling in patients with chronic neutrophilic leukemia, a rare cancer with few treatment options and a high rate of relapse. Her goal is to identify new, targetable signaling proteins that could open the door for better treatments.

Ranish Patel M.D., a surgical resident in the OHSU School of Medicine, received an Early Clinical Investigator Award from the Medical Research Foundation of Oregon. The $30,000 award is supporting his research evaluating a potential blood-based biomarker for early detection of pancreatic cancer.

Megan Ruhland, Ph.D., will help map the proteome of senescent cells and their tissue microenvironment at single-cell resolution in a project awarded $475,000 from the National Institutes of Health. Senescent cells can contribute to cancer and other aging-related diseases. The project leader is Ying Zhu, Ph.D., at Pacific Northwest National Laboratory.

CEDAR scientist Josh Saldivar, Ph.D., secured an R35 award from the National Institute of General Medical Sciences. The 5-year, $1.9 million award supports his lab’s efforts to uncover how cells coordinate DNA replication, transcription and chromatin re-establishment during cell division, processes that become disrupted in cancer.

Jennifer Saultz, D.O., is one of 11 basic and translational junior faculty selected for a Scholar Award from the American Society of Hematology. She is working to improve current treatment strategies and response rates in patients with acute myeloid leukemia.

Evan Shereck, M.D., M.Ed., received the Edward J. Keenan Faculty Award for Distinguished Teaching of Medical Students. She is associate director for cancer research training in the Knight Cancer Institute and director of the Pediatric Hematology/Oncology Fellowship Program.

Evan Shereck, left, receives the Edward J. Keenan Faculty Award for Distinguished Teaching of Medical Students from Tomo Ito, Ed.D., assistant dean for curriculum, Undergraduate Medical Education Program (OHSU/Jordan Sleeth)

Palliative care surgeon Timothy Siegel, M.D., received the Leonard Tow Award for Humanism in Medicine presented by The Arnold P. Gold Foundation. The award recognizes faculty members and medical students who are judged by their peers to exemplify the humanistic qualities of a physician. Siegel is an assistant professor of medicine, Division of Hematology and Medical Oncology. He leads the only rotation in the country where a surgical intern spends a full month working on the palliative care team.

The Prostate Cancer Foundation is supporting Alexandra Sokolova, M.D., with the 2022 John & Daria Barry-PCF VAlor Young Investigator Award. Sokolova and team are aiming to improve genetic testing of family members of veterans with prostate cancer who carry heritable prostate cancer risk mutations. Approximately 12% of patients with metastatic prostate cancer carry heritable mutations that contributed to their disease. Sokolova’s project will evaluate provider-initiated cascade genetic testing as an effort to increase the numbers of family members who get tested and improve equity and equality in access.

Deanne Tibbitts, Ph.D., was selected as a scholar in the Oregon Building Interdisciplinary Research Careers in Women’s Health program. The two-year award will provide salary and research support for her project aiming to better understand why women experience more immune-related adverse events than men in response to immunotherapy for cancer.

The National Cancer Institute issued a $6.5 million, five-year award to Jeffrey Tyner, Ph.D., Shannon McWeeney, Ph.D., and Brian Druker, M.D., to establish a center in the Acquired Resistance to Therapy Network (ARTNet). The goal of their project is to understand the biological drivers of acquired drug resistance in acute myeloid leukemia, identify new drug combinations to prevent drug resistance and improve outcomes for patients with AML.

And Shannon McWeeney, Ph.D., began co-leading tool development for a $7.8 million project in the National Institutes of Health Bridge2AI program, which supports the adoption of artificial intelligence in biomedical research. The project is aimed at generating new biomedical and behavioral data sets that are ethically sourced, trustworthy, well-defined and accessible. It is one of three Bridge2AI projects with OHSU co-leaders. 

Jason Webb, M.D., is a co-investigator in a $2.6 million study funded by the Patient Centered Outcomes Research Institute evaluating “primary palliative care” delivered by oncology clinicians to see how it compares with palliative care provided by specialists for patients with acute myeloid leukemia. The principal investigators are at Massachusetts General Hospital. Webb is an associate professor of medicine and psychiatry, and he heads the palliative care section in the School of Medicine.

Patrick J. Worth, M.D., is among the first recipients of the National Cancer Institute’s Early-Stage Surgeon Scientist Award. He is one of 12 selected from across the U.S. for this career development program. The assistant professor of surgery also received an Idea Development Award from the Department of Defense Pancreatic Cancer Research Program. His proposal is one of 12 selected out of 219 applications. The three-year award will fund his research on the underpinnings of rapid recurrence of pancreatic cancer.

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