Knight Cancer Institute signal achievements of 2020

In a year overshadowed by the coronavirus pandemic, the OHSU Knight Cancer Institute’s people adapted and accomplished many great things. From basic research, to patient care, to impact in the community, the institute has a mission to end cancer as we know it. Here’s a look back at a year of significant achievements amid unprecedented challenges.

Leading the way

Targeting an aggressive leukemia: The Beat AML clinical trial showed that it’s feasible and safe to take time for DNA sequencing to target therapies against fast-moving acute myeloid leukemia. Patients who opted for the precision medicine approach experienced a lower early death rate and superior overall survival compared with patients who opted for standard of care. Knight Cancer Institute Director Brian Druker, M.D., helped plan and develop the trial and OHSU was among the top four sites for enrolling subjects. The study emerged from a collaboration started in 2013 by the Knight Cancer Institute and The Leukemia & Lymphoma Society.

Charles Thomas Jr., M.D.

Building diversity: Racial and ethnic minorities remain vastly underrepresented in medical subspecialties despite decades of national workforce-diversity efforts. This shows the extent of resistance to diversification in these fields, asserts a New England Journal of Medicine article co-authored by OHSU’s Charles Thomas, Jr., M.D. He and Kemi Doll, M.D., at the University of Washington presented solutions that can be deployed at the division or department level to cultivate the retention and promotion of underrepresented-minority faculty.

Partnering to accelerate new therapies: The OHSU Knight Cancer Institute is one of nine centers worldwide (and one of three in the U.S.) selected to join AstraZeneca’s Partner of Choice Network. “Through this important collaboration, we will have access to the latest drugs, and clinical trial data, to help ensure our patients have access to cutting edge treatment options,” said Gordon Mills, M.D., Ph.D., director of the OHSU Knight Cancer Institute’s precision oncology program. OHSU also formed a collaboration with Ionis Pharmaceuticals to develop new drugs for blood cancers including acute myeloid leukemia, one of the most difficult to treat. “There are many genes that are essential to the biology of leukemia for which no drugs exist,” said Knight Cancer scientist Julia Maxson, Ph.D. “This collaboration expands the realm of genes that can be targeted therapeutically and will fundamentally advance our mission of harnessing scientific discoveries to help patients.”

Inspiring philanthropy: A $10 million donation from Tim Boyle, CEO of Columbia Sportswear, and his wife, Mary, is supporting the new OHSU-University of Oregon Center for Biomedical Data Science. Initial projects of the partnership will focus on cancer, and the center will help advance the OHSU Knight Cancer Institute’s two primary research initiatives: precision oncology and precision early cancer detection.

Recruiting top leaders: A husband-wife team known for specializing in cancer drug development at Stanford University joined the OHSU Knight Cancer Institute in July. Shivaani Kummar, M.D., heads the Division of Hematology and Medical Oncology in the OHSU School of Medicine. Sanjay Malhotra, Ph.D., Kummar’s spouse, established the Knight Cancer Institute’s new Center for Experimental Therapeutics, which he co-leads with Kummar. The School of Medicine also hired Jason A. Webb, M.D., a national leader on integrating palliative medicine and oncology formerly at Duke University. Webb is chief of the Palliative Care Section in the Division of Hematology and Medical Oncology, associate professor and member of the Knight Cancer Institute.

 


Responding to COVID-19

When the pandemic arrived, the Knight Cancer Institute quickly found ways to maintain access to clinical trials of new cancer therapies. “One of the most surprising things to me was how rapidly we were able to pivot toward telehealth. Within a week or so, we made a wholesale shift and were able to care for and interact with our patients in a new way,” Deputy Director Tom Beer, M.D., told Portland’s Business Tribune. “Across all cancer disease groups, we have over 200 trials actively enrolling and about 75% of those utilized telehealth when appropriate.”

Tom Beer, M.D. (OHSU/Kristyna Wentz-Graff)

OHSU is one of five clinical trial sites investigating a blood test for cancer early detection developed by GRAIL, Inc., and OHSU has continued to enroll participants safely during the pandemic. The GRAIL blood test is being evaluated for its ability to detect more than 20 types of cancer, including types for which no screening methods exist. “Through OHSU’s participation, people in Oregon are among the first to have the opportunity to be tested,” Beer said.

Before the pandemic, cancer survivors had been gathering multiple times a week for group exercise sessions in National Cancer Institute-funded studies led by Kerri Winters-Stone, Ph.D. Within 72 hours of halting in-person sessions, her team organized the means for participants to continue exercising together virtually by videoconference. The team is conducting study assessments, such as balance and strength testing, virtually, as well, so they can benchmark participants’ progress from exercise. Going virtual has allowed them to expand access and enroll participants in California, Idaho and Nevada.

The Knight Cancer Institute’s Community Partnership Program helps Oregon communities address cancer needs, but this year the program put out a special call for COVID-19 proposals and funded 14 projects responding to the pandemic. Grants are supporting food security, COVID-19 outreach, technology to promote social distancing guidelines, and more. (An earlier round of grants supported 13 cancer projects, many focused on prevention efforts such as tobacco cessation and HPV vaccination.)

In August, the Knight’s Center for Experimental Therapeutics was awarded one of eleven grants from the Indo-U.S. Science and Technology Forum (IUSSTF) to become a virtual network for COVID-19 research. In September, the Knight and 16 other cancer centers began working with the National Cancer Institute to better understand the consequences of the pandemic for cancer prevention, treatment, and survivorship. The goal is to guide cancer prevention and control strategies to combat the ill effects of the pandemic, particularly among medically underserved populations.


 

Delivering discoveries

Advancing immunotherapy for prostate cancer: Restoring tumor-specific immunity is a treatment strategy that has worked well, but only against some cancers. Research led by OHSU oncologist Julie Graff, M.D., revived hope that the approach may help men with life-threatening prostate cancer. And this year Graff began leading an international phase 3 clinical trial. That study is open and enrolling at OHSU and a multitude of other trial sites. Graff is the global principal investigator.

Julie Graff, M.D. (OHSU Foundation)

Big window for early detection: For many types of cancer, OHSU research suggests there is a large window of time in which to find smoldering tumor cells and eliminate them before they become life-threatening. Errors in DNA that trigger the start of some of these deadly cancers can arise a decade or more before tumors appear. The findings fit with what is known about the few kinds of cancer in which researchers have worked out the timing of progression. In colon cancer, for instance, pre-cancerous growths called polyps form 10 to 15 years before giving rise to malignant tumors. “Our new data show that the timing can be similar in cancers without detectable premalignant conditions, such as ovarian cancer, raising hope that these tumors also can be identified in pre-cancerous stages,” said co-author Paul Spellman, Ph.D., a professor of medicine (hematology and medical oncology) in the OHSU School of Medicine.

Immune cell therapy and quality of life: CAR-T-cell therapy for lymphoma not only extends survival, it may also improve quality of life after treatment, according to a study led by OHSU’s Richard Maziarz, M.D., medical director of the adult blood and marrow stem cell transplant and cellular therapy program in the Knight Cancer Institute. CAR stands for “chimeric antigen receptor” and the treatment is a form of immunotherapy in which the patient’s immune system T cells are collected, genetically engineered to target cancer and then infused back into the patient.

Perturbed tumors reveal their secrets: Researchers have mapped in rich detail how cancer cells of many types adapt when challenged with an array of targeted drugs. And they’ve made all of the data freely available to other scientists via a user-friendly web portal. “This is the largest data set of its type in existence,” said Gordon Mills, M.D., Ph.D., a senior author of the paper in the journal Cancer Cell describing the work. The data set has already provided support for many of the drug combinations that are being tested in clinical trials at the Knight Cancer Institute.

Expanding treatment options for rare cancers: OHSU enrolled more participants than any other center in the phase 1 trial of avapritinib, approved for the treatment of adults with unresectable or metastatic GIST with a mutation making them resistant to all previously available drugs. “For the first time, we can offer these patients a highly effective treatment that targets the underlying genetic cause of their disease,” said Michael Heinrich, M.D., a professor of medicine in the Division of Hematology and Medical Oncology.

Michael Heinrich, M.D., left, talks with Diana Dowd, center and her friend Lauri Roskamp, during an appointment. Dowd took part in a clinical trial of the drug avapritinib. (OHSU/Kristyna Wentz-Graff)

Understanding the aggressive breast cancers missed by mammograms: About 20% to 30% of women with breast cancer have tumors that are missed by mammogram screening. And these interval breast cancers – discovered between routine mammograms – seem to be more lethal than those detected by screening. A new study by Oregon researchers revealed that survival is worse only if the interval cancer appears within one year after a mammogram that did not detect cancer. “Current screening strategies are not good enough to identify these interval breast cancers,” said co-author Zhenzhen Zhang, Ph.D., M.P.H., an assistant professor of medicine (oncological sciences) in the OHSU School of Medicine. “We need more research to find a better way to find them in time.” The researchers are establishing an interval breast cancer registry to expedite efforts to find biomarkers to identify those at high risk.

Mapping the cancer ecosystem to find cures: The Human Tumor Atlas Network is a massive effort to map the complex ecosystems of cancer – and pave the way for advances in prevention, early detection and treatment. The components of the network and how they are coming together were detailed in a perspective article in the journal Cell by project leaders including including Joe Gray, Ph.D.Gordon Mills, M.D., Ph.D., Jeremy Goecks, Ph.D., and George Thomas, M.D., in the Knight Cancer Institute. The project will give researchers tools to explore tumor ecosystems in multiple dimensions and visualize their structure, composition, and interactions at distinct points in tumor evolution. The point is to help researchers find new and better predictive biomarkers and reveal cell types, cell states, and cellular interactions that can be targeted for therapy.

Lighting up nerves to prevent damage during surgery: Sparing nerves from injury remains a huge problem for surgeons. Knight Cancer researchers have developed a possible solution: nerve-specific fluorescent dyes that allow operators to view nerves deeper within tissues than previously possible. “Having a way to see nerves during surgery could significantly decrease injuries,” said Summer Gibbs, Ph.D., an OHSU associate professor of biomedical engineering.

Stopping the secretive cells that revive deadly tumors: Cancers are notorious for their ability to rebound uncontrollably after a first round of successful treatment. Knight Cancer researchers have uncovered how a fraction of a tumor’s cells conspire with the immune system to establish an inviting niche for the growth of new tumors that are resistant to anti-cancer drugs. “Our main focus is finding out how we can prevent tumor recurrence,” said senior author Naoki Oshimori, Ph.D., an assistant professor of cell, developmental and cancer biology in the OHSU School of Medicine.

 

Serving the community

For veterans with prostate cancer, a new center of excellence: VA Portland Health Care System and OHSU are launching a precision oncology center of excellence supported by the Prostate Cancer Foundation. On Veteran’s Day, the foundation announced $5 million in funding for new centers in Portland and in Boston. “This award will make it possible for us to reach out to veterans throughout Oregon and Southwest Washington to offer genetic testing and sequencing for all patients with metastatic prostate cancer,” said Julie Graff, M.D., section chief of Hematology/Oncology at VA Portland, and associate professor in the OHSU School of Medicine.

Extending radiation oncology to underserved regions: Knight Cancer physicians are making radiation therapy available far from urban centers by means of local partnerships. Charles Thomas, Jr., M.D., chair of the OHSU Department of Radiation Medicine, and Pehr Hartvingson, M.D., chief medical officer at the CMH-OHSU Knight Cancer Collaborative in Astoria recounted their progress in an OHSU podcast.

Top designation for lymphatic disease care: OHSU qualified as a comprehensive center of excellence in the care of lymphatic disease, one of 11 institutions in the world to earn the designation. The centers of excellence program aims to increase access to the best possible multi-disciplinary care for lymphatic diseases such as lymphedema that can develop after cancer surgery and radiation. Comprehensive centers have proven capable of coordinating a full range of clinical care and support services, all within the same institution. Plastic and reconstructive surgeon Allison Nauta, M.D., directs the Lymphedema Program at OHSU.

Helping patients access newest treatment options: Knight Cancer Institute patient Lisa Wooden became the second in the U.S. to be treated with a device that uses electromagnetic energy to disrupt cell division in tumors. It’s the first new FDA-approved treatment option for mesothelioma in 15 years. OHSU was the third site in the country certified to offer the treatment. Wooden’s mesothelioma cancer was diagnosed at an advanced stage. “My goal is to be here as long as I can for my family and friends,” she said. “Everybody could use hope these days; everyone could use encouragement.”

Lisa Wooden with her husband, Peter Hansen. (Lisa Wooden)

Understanding cancer genetic risks: The Healthy Oregon Project, a statewide research study of Oregonians’ genetic cancer risks, received a $6.1 million award from the National Institutes of Health. The OHSU Knight Cancer Institute study is enlisting participants across Oregon to undergo no-cost genetic cancer screening using a saliva sample and to complete additional surveys about their environment, behaviors, and lifestyle to understand their health risks. More than 4,700 people have volunteered to participate in the study since it began in 2018.

 

Garnering honors

  • CEDAR distinguished scientist Bruce Branchaud, Ph.D., was elected a Fellow of the National Academy of Inventors. “This distinction is particularly meaningful to me as it represents how applied technology can impact the greater good,” Branchaud said. “It exemplifies CEDAR’s mission: to focus on the development of truly impactful real-world solutions for the early detection of cancer.”
  • Ted Braun, M.D., Ph.D., who is working to define early events in a life-threatening leukemia, is the winner of a Scholar Award from the American Society of Hematology. Braun is an instructor of hematology and medical oncology in the OHSU School of Medicine. He is one of 13 from across the U.S. and Canada chosen as Basic/Translational Fellows by the American Society of Hematology.
  • Amanda Bruegl, M.D. (OHSU/Kristyna Wentz-Graff)

    OHSU gynecologic oncologist Amanda Bruegl, M.D., was named a scholar of the Harold Amos Medical Faculty Development Program, which is part of The Robert Wood Johnson Foundation. The four-year fellowship will help Bruegl advance her research on the disproportionate burden of cervical cancer among Native American women. Bruegl is an assistant professor of obstetrics and gynecology in the School of Medicine.

  • CEDAR distinguished scientist Beverly Emerson, Ph.D., joined an accomplished roster of scholars, artists, and all-around leaders who were elected fellows of the American Academy of Arts & Sciences. The 2020 class of fellows includes singer-songwriter-activist Joan Baez, former Attorney General Eric Holder, novelist Ann Patchett, and indie filmaker Richard Linklater.
  • The Chan Zuckerberg Initiative awarded funding to Jeremy Goecks, Ph.D., a leader in helping biomedical scientists work with massive amounts of data and share findings more openly. His work also received funding from the National Cancer Institute. Goecks is an associate professor of biomedical engineering in the OHSU School of Medicine and he directs computational biology for the Knight Cancer Institute’s precision oncology program.
  • Joe Gray, Ph.D., and Paul Spellman, Ph.D., are among the recipients of the 2020 AACR Team Science Awards for their work on The Cancer Genome Atlas, which has analyzed more than 20,000 patient and control samples to characterize the genetic roots of 33 cancer types. Gray is a professor of biomedical engineering in the OHSU School of Medicine and the Knight Cancer Institute’s associate director for biophysical oncology. Spellman is a professor of molecular and medical genetics and co-director of CEDAR.
  • Susan Hedlund, M.S.W., LCSW, OSW-C, and Caroline Macuiba, LCSW, OSW-C, were selected to serve on an advisory committee for a national survey on the role of oncology social workers in the delivery of quality cancer care. It’s part of an initiative from the University of Michigan School of Social Work, in collaboration with the Association of Oncology Social Work.
  • Cancer scientist Lillian Klug, Ph.D., received the Young Female Sarcoma Leadership Award from the Life Raft Group, a national nonprofit supporting patients with a rare cancer called gastrointestinal stromal tumor, or GIST. Klug is research project manager in the Heinrich Lab.
  • Dermatologist Olivia M. Lucero, M.D., won the Lasker Foundation’s essay contest. The New York-based foundation started the essay contest in 2014 to engage young scientists in discussions about the role biomedical research plays in society. Lucero is a post-doctoral fellow in the Druker lab and researches targeted therapies for cutaneous and hematological malignancies.
  • The Endocrine Society honored CEDAR scientist Hisham Mohammed, Ph.D., with its Early Investigators Award for his work exploring the regulation of hormone-driven cancers. Mohammed is an assistant professor of molecular and medical genetics in the OHSU School of Medicine.
Hisham Mohammed, Ph.D. (OHSU Foundation)
  • Cell Press listed Joshua Saldivar, Ph.D., among 100 inspiring Hispanic/Latinx scientists. The list aims “to put an end to the harmful myth that there are not enough diverse scientists to give seminars, serve as panelists, or fill scientific positions,”  the editors said, adding “we hope it will help to change the perception of what a scientist looks like and makes our collective image more representative of society at large.” Saldivar is an assistant professor in the OHSU School of Medicine’s Division of Oncological Sciences.
  • Mara Sherman, Ph.D., is one of five leading early-career cancer scientists across the U.S. named as a Pew-Stewart Scholar for Cancer Research. Sherman is an assistant professor of cell, developmental and cancer biology in the OHSU School of Medicine. Her award-winning work is uncovering the role of non-cancer cells that support tumor growth in pancreatic ductal adenocarcinoma.
  • The SWOG Cancer Research Network and The Hope Foundation for Cancer Research gave Charles R. Thomas, Jr., M.D., the inaugural SWOG Special Recognition Award for Mentorship. “His generosity with his time, knowledge, and connections is legendary,” one nominator said. Thomas is professor and chair of the Department of Radiation Medicine in the OHSU School of Medicine.
  • Physician-scientist Reid Thompson M.D., Ph.D., received the ASTRO-Melanoma Research Alliance Young Investigator Award for his research on melanoma. Thompson, an assistant professor of radiation medicine, is studying the use of blood tests for circulating tumor DNA as a way to monitor disease progress and response to treatment. He is focusing on cases in which the melanoma has metastasized and some of the secondary tumors have developed resistance to drug therapy.
  • Jeff Tyner, Ph.D., received the Emerging Leader Award from The Mark Foundation for Cancer Research. Tyner is a professor of cell, developmental and cancer biology in the OHSU School of Medicine. He and his team are seeking combinations of anticancer agents tailored to the vulnerabilities of different subsets of acute myeloid leukemia. Tyner also won a Faculty Excellence and Innovation Award. The new $750,000 award supports early- and middle-stage investigators at OHSU.

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