Knight Cancer signal achievements of 2021

In a year that was anything but normal, the OHSU Knight Cancer Institute’s people stepped up and continued to do 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 the ongoing pandemic.

 

Delivering discoveries

Improving survival in advanced prostate cancer: A new kind of prostate cancer treatment tested at OHSU combines a targeting compound with a radioactive isotope to irradiate and kill cancer cells, sparing most normal tissues. “This is a completely new treatment option that extends life and disease control in metastatic castration-resistant prostate cancer – the most aggressive and deadly type,” said Knight Cancer Institute Deputy Director Tom Beer, M.D., who helped lead the clinical trial and co-authored the New England Journal of Medicine report on the study establishing the new treatment for men with prostate cancer that has spread and become resistant to hormone therapy.

Pepper Schedin, Ph.D.

Understanding uniquely dangerous postpartum breast cancers: Breast cancers that emerge within five to ten years of pregnancy are more likely to become life-threatening. New research led by Pepper Schedin, Ph.D., found that these postpartum breast tumors represent a unique subtype of cancer that could require different treatments than other breast cancers. “For women diagnosed in that time window, they might have better outcomes if they had therapies targeted to the unique features of their tumors, which have been unknown until now,” said Schedin, a professor in the Department of Cell, Developmental & Cancer Biology in the OHSU School of Medicine.

New target for fighting cancers: Researchers including OHSU’s Stephen Spurgeon, M.D., verified a much-needed new target for treating cancers that often become resistant to existing therapies and become deadly. In an early-phase clinical trial at OHSU and other centers, a therapy targeting the cell-surface receptor ROR1 shrank tumors fully or partially in 60% of subjects with one type of cancer and 47% with another type, providing the first clinical evidence that ROR1 is a valid target. “This lays the foundation for a novel cancer therapy target for a patient population that is truly in need, without a lot of other options,” said Spurgeon, senior author of the study, published online in NEJM Evidence.

Expanding options for people with liver cancer: People with liver cancer awaiting transplantation could benefit from non-invasive radiation treatments but are rarely given this therapy, according to a new analysis of U.S. national data. “External-beam radiation therapy is a proven, established, safe and effective treatment option for patients with unresectable liver cancer, yet its under-utilization within this population—fewer than 4% of patients—highlights a real-world gap in treatment options available for patients with hepatocellular carcinoma,” study author Nima Nabavizadeh, M.D., told reporters at the American Society for Radiation Oncology Annual Meeting. Nabavizadeh is an associate professor of radiation medicine at Oregon Health & Science University in Portland.

Making cancers vulnerable to immunotherapies: Immune checkpoint inhibitors can bring dramatic, life-saving results – but only for a limited fraction of people with cancer. Aiming to help more patients benefit, researchers led by Wassana Yantasee, Ph.D., developed a therapeutic vaccine that broadly expands the tumor-stopping power of checkpoint inhibitors. PDX Pharmaceuticals, founded by Yantasee, was awarded two grants totaling $4.3 million from the National Cancer Institute to develop the therapeutic vaccine. Yantasee is a professor of biomedical engineering in the OHSU School of Medicine.

New clues to what turns prostate cancers deadly: Only a fraction of prostate cancers become life threatening, but it’s impossible to predict which ones. In a surprising new study, Knight Cancer researchers found that two signaling proteins used by nerve cells can become active in and around prostate tumors – and might play a role in driving the cancers to turn deadly. The two proteins, in a class known as neuronal adhesion molecules, take part in conveying signals between nerve cells. “Based on our findings, we propose that the expression of neuronal adhesion molecules in prostate cancer cells mark tumors for a more aggressive, potentially metastatic phenotype,” said principal investigator Sebnem Ece Eksi, Ph.D., a post-doctoral scholar at CEDAR, the Knight’s Cancer Early Detection Advanced Research Center.

Anne Matsen had already faced two cancers, lymphoma in 2006 and leukemia in 2008, when she was diagnosed last year with pancreatic cancer. Her need for complex Whipple surgery led her to Flavio Rocha, M.D., even following him from Seattle to OHSU when he was recruited here in 2021. Read the full story.

Stopping resistant ovarian cancer: Researchers led by OHSU’s Sanjay Malhotra, Ph.D., have discovered a way to target a pivotal driver of drug resistance in ovarian cancer, one of the top causes of cancer death in women. The experimental compound, called SU056, shrank tumors and stopped the rise of metastatic tumors in animal models of ovarian cancer. “We have subsequently shown its effectiveness in models of six different cancer types,” said Malhotra, director of the Center for Experimental Therapeutics in the Knight Cancer Institute.

Unlocking the combination to target evasive kidney cancers: Roughly one in four people with kidney cancer have a type that does not respond to targeted therapy drugs, leaving no proven treatment options for those whose tumors have started to spread. “It’s very much an unmet need,” says George Thomas, M.D., whose research team has discovered a potential way to stop these cancers by combining two different targeted agents. Individually, neither drug has much impact. Working together, they suppress a key cancer signaling pathway and shrink tumors in animal models of the cancer, called non-clear cell renal cell carcinoma.

New views into single cells of cancer: Knight Cancer scientists devised a way to zero in on the subpopulations of cells within a tumor that drive important disease behaviors, such as drug resistance and metastasis. “If we can precisely identify which cell subpopulations are responsible for drug response, tumor progression and metastasis, then we can look deeper to identify the mechanisms and develop better targeted therapies,” said Zheng Xia, Ph.D., senior author of a paper in Nature Biotechnology describing the new method.

Jamming fat metabolism stops blood cancer cells: Targeted cancer therapies work by blocking specific, cancer-driving mutations. New research by Daniel Liefwalker, Ph.D., shows that cancers driven by several different mutations can all be stopped by a targeting a shared growth pathway that they use to fuel their nonstop cell division. “This seems to be a common metabolic strategy that is exploitable as a target for cancer therapy,” said Liefwalker, principal author of a paper in the journal Cancer & Metabolism describing the discovery. Liefwalker is a research assistant professor in the OHSU School of Medicine.

Safely preventing dangerous blood clots: Conventional anti-clotting drugs have a big downside: increased risk of internal bleeding. An entirely new class of antithrombotic developed at OHSU aims to eliminate bleeding complications.  A phase 2 clinical at OHSU is testing whether the drug works in preventing catheter-associated blood clots in patients with cancer receiving chemotherapy, said principal investigator Joseph Shatzel, M.D. The investigational drug, xisomab 3G3, is a recombinant antibody that binds to a specific site on a blood enzyme called factor XI. When bound there, it blocks the activation of factor XI by another blood clotting factor, XII, which interrupts the intrinsic contact activation pathway of blood coagulation. But the antibody does not stop factor XI from contributing to the extrinsic pathway that is vital for rapid clotting of blood at wound sites.

Shedding light on early-onset colorectal cancer: The rapid rise of colorectal cancer in younger people remains perplexing, but an OHSU study fills in a missing piece of the puzzle. Researchers found that three genes involved in immunity and inflammation are more active in and around tumors in early onset colorectal cancer. Experiments showed how these upregulated genes interact with other genes to reshape the immune environment for colorectal cancer. “Our findings suggests that the immune system in younger patients is actually failing at mounting a good response against these tumors,” said senior author Sudarshan Anand, Ph.D., an associate professor of cell, developmental and cancer biology.

Overcoming drug resistance to stop a deadly blood cancer: Knight Cancer researchers have discovered a potential way to make targeted therapy drugs more effective and longer lasting for people with acute myeloid leukemia. AML is a fast-advancing blood cancer and one of the most difficult to treat. The need for better therapies is critical. “Understanding the biology of early resistance may offer new opportunities to prevent or delay late resistance and improve clinical outcomes,” said first author Sunil Joshi, Ph.D., a medical student in the OHSU School of Medicine who completed his doctoral degree under the mentorship of Brian Druker, M.D., Elie Traer, M.D., Ph.D., and Cristina Tognon, Ph.D.

Sunil Joshi, Ph.D. (OHSU/Joe Rojas-Burke)

 

Serving the community

Expanding access to experimental cancer treatments: In August, the Knight Cancer Institute opened a new, 13,000-square-foot space devoted to serving patients taking part in early-phase clinical trials. The unit completes the build-out of the cancer clinic at OHSU’s Center for Health and Healing Building 2 in Portland’s South Waterfront District. Its staff of physicians, nurses, pharmacists, data coordinators and clinical research coordinators are trained and experienced in caring for people participating in cancer clinical trials. Shivaani Kummar, M.D., head of the Division of Hematology and Medical Oncology, talked with Cancer Translated about the impact of early phase clinical trials and how OHSU’s new Early Phase Clinical Trials Unit will give more people access to experimental cancer treatments in Portland.

Shivaani Kummar, M.D., FACP, talks with OHSU Knight Cancer Institute Director Brian Druker, M.D., at the opening of the institute’s early-phase clinical trial unit. (OHSU/Joe Rojas-Burke)

Delivering exercise medicine to cancer survivors: Before the pandemic, cancer survivors gathered multiple times a week for group exercise sessions in National Cancer Institute-funded studies led by Kerri Winters-Stone, Ph.D. To continue during the pandemic, she and her team adapted the training for live, online delivery. They published a journal article describing how the virtual group training sessions could enhance efforts to integrate evidence-based exercise medicine into standard oncology care.

Cutting-edge treatment for veterans: Denied coverage by his private health insurance, an Army veteran with prostate cancer gained access to an advanced immunotherapy drug thanks to a Knight Cancer Institute doctor and the VA Portland Health Care System. The veteran, David Atkinson, had been participating in a clinical trial at OHSU led by Julie Graff, M.D., when his cancer worsened and his health plan declined to authorize the FDA-approved off-study treatment. Graff, an associate professor in the OHSU School of Medicine, instructed her team to arrange for his enrollment in VA Portland, where she’s the section chief of hematology and oncology. “We are taking more patients from outside VA who may be eligible for benefits and getting them enrolled quickly, specifically when they have cancer,” Graff told VA Research Currents.

Support after a life-threating cancer diagnosis: Close to a third of patients with acute myeloid leukemia experience significant symptoms of post-traumatic stress disorder, according to a study co-authored by the Knight Cancer Institute’s Jason A. Webb, M.D. The findings underscore the need to screen for PTSD in these patients, and to develop strategies to help them cope with the trauma of their diagnosis and treatment. Web is an associate professor in the OHSU School of Medicine and chief of the Palliative Care Section in the Division of Hematology and Medical Oncology. He has been studying the impact of integrating palliative care early during the care of people living with cancer, and optimizing the management of cancer pain and psychological distress.

Fulfilling local cancer-related needs: The Knight Cancer Institute’s Community Partnership Program funded a dozen more locally-led projects across the state. They aim to prevent lung cancer, increase understanding of pancreatic cancer risk, and provide resources to patients with cancer in rural Oregon. The program offers multiple tiers of funding to help local organizations identify cancer-related needs and create solutions. Since its establishment in 2014, the program has awarded more than $4.3 million to 164 projects.

Healthy Oregon Project reaches 20,000 participants: Launched in 2018, HOP is working to understand how genetics and lifestyle change our vulnerability to cancer and other chronic diseases. Participants complete health surveys and receive saliva-based screening tests for DNA mutations known to increase risk. OHSU Knight Cancer Institute investigators Paul Spellman, Ph.D., and Jackie Shannon, Ph.D., created and lead the study.

HOP team members Carol Halsey, Casey Conrad, Katie Johnson-Camacho and Vanessa Serrato assemble and package kits in the Knight Cancer Research Building.

 

Leading the way

Top performer for CAR T therapies and stem cell transplants: The Knight Cancer Institute’s immunotherapy and cell transplant team earned national recognition for its expertise and experience providing CAR T-cell therapy — the breakthrough treatment for children with leukemia and for adults with certain hard-to-treat blood cancers. Emerging Therapy Solutions, a firm that helps healthcare payers manage the risks associated with high-cost therapies, analyzed volume and outcomes data to determine which providers have the most experience with CAR T-cell therapy and with stem cell transplants. The Knight’s immunotherapy and cell transplant team has performed more than 4,500 bone marrow and stem cell transplants in adults and children, putting OHSU among the top 20 centers in the U.S. by number of procedures. The team’s Eneida Nemecek, M.D., and Richard Maziarz, M.D., co-authored an international state-of-the-science report in November, reviewing the highest priority questions in hematopoietic stem cell transplant and cell therapy.

Advancing multi-cancer early detection: Before cancers become deadly, signs of their presence can show up in escaped strands of DNA and other tell-tale molecules. Technical leaps are making it possible to find these signals in blood, saliva, urine and even exhaled breath.  A new consortium with the OHSU Knight Cancer Institute and other leading cancer institutions aims to pave the way for clinical use of technologies to screen healthy people for many kinds of cancer all at once. At the American Society of Clinical Oncology Annual Meeting in June, OHSU’s Tom Beer, M.D., presented clinical trial results with a blood test able to detect more than 50 types of cancer. “Most importantly, it can detect cancers that have no recommended screening tests today, and more than two-thirds of cancers go unscreened for this reason,” Beer told news reporters.

Tom Beer, M.D., deputy director of the OHSU Knight Cancer Institute (OHSU/Kristyna Wentz-Graff)

NCI-designated Comprehensive Cancer Center: The Knight Cancer Institute this year renewed its Comprehensive Cancer Center status with the National Cancer Institute, and it remains the only cancer center with that designation between Sacramento and Seattle. To earn the NCI’s top rating, centers must meet stringent criteria in three key areas: laboratory research, clinical research and population-based science. Comprehensive Cancer Centers have to demonstrate a proven aptitude in research that bridges these scientific areas, serves the broader population, and integrates training and education of biomedical researchers and health care professionals.

Lisa Coussens, Ph.D.

OHSU cancer scientist chosen to lead at AACR: The American Association for Cancer Research, a venerable organization with 48,000 members in 127 countries, elected Lisa M. Coussens, Ph.D., as their president-elect for 2021–22. The professor and chair of the Department of Cell, Developmental and Cancer Biology was also named a Komen Scholar, one of six chosen by the Susan G. Komen Breast Cancer Foundation to lead peer review for the foundation’s $1.1 billion research program and provide scientific expertise and guidance. “Dr. Coussens is an extraordinary scientist whose pioneering research on the tumor microenvironment and chronic inflammation has had an incredible impact on the understanding and treatment of many different types of cancer,” said AACR Chief Executive Margaret Foti.

Among the world’s most influential scientists: Seven OHSU scientists are among the world’s most highly cited, including two Knight Cancer Institute members: Lisa Coussens, Ph.D., and Gordon Mills, M.D., Ph.D. That’s according to the consulting and data analysis firm Clarivate, which compiles an annual list of researchers who have demonstrated significant and broad influence reflected in the publication of multiple papers frequently cited by their peers.

Inspiring philanthropy: The Kuni Foundation awarded $1.5 million to support the Knight Cancer Institute’s SMMART clinical trials platform and a further $1 million to support the Knight Scholars, which mentors high school students from communities underrepresented in science, medicine and public health. “We’re proud to support the OHSU Knight Cancer Institute’s programs to diversify the cancer research workforce and targeted science that improves detection and treatment for people of color,” said Kuni Foundation President Angela Hult.

Valuable recognition for OHSU’s Molecular Genetic Pathology Fellowship: OHSU’s Molecular Genetic Pathology Fellowship received a grant from NeoGenomics Laboratories to support fellows for the 2021-22 and 2022-23 academic years in the Knight Cancer Institute’s Knight Diagnostic Laboratories. Launched in 2002 by the Department of Pathology and Laboratory Medicine, the MGP Fellowship trains physicians with expertise in molecular diagnostics who will become clinical consultants on the applications of molecular pathology to a wide variety of clinical settings – with a primary focus on advanced cancer diagnostics. It was among the first molecular genetic pathology fellowships in the U.S., and competition for slots is highly selective.

Collaborating for early detection: Nearly 500 scientists, students and biotech leaders gathered online for the Early Detection of Cancer Conference from Oct. 6-8., presented by the OHSU Knight Cancer Institute, Cancer Research UK and the Canary Center at Stanford. The conference is part of a long-term commitment to invest in early detection research, to understand the biology behind early-stage cancers, find new detection and screening methods, and enhance uptake and accuracy of screening.

‘Game-changer’ cancer drug celebrates 20 years: Ushered from lab to clinical success by Brian Druker, M.D., director of the OHSU Knight Cancer Institute, imatinib (brand name: Gleevec) transformed the outlook for people with chronic myeloid leukemia — and paved the way for other targeted therapies. May 10 marked the 20th anniversary of the drug’s approval by the U.S. Food and Drug Administration, prompting major news media and scientific journals to reflect on the enduring impact of the cancer drug that “changed everything”.

Knight Cancer Institute Director Brian Druker, M.D. (OHSU/Kristyna Wentz-Graff)

 

Garnering honors

Lifetime Achievement Award for oncology social worker: Nancy Boyle, LCSW, OSW-C, was the first social worker in OHSU’s bone marrow transplant program and has been with the program since its inception. She was honored this year with the Hematology-Oncology Lifetime Achievement Award from The Leukemia & Lymphoma Society. Boyle retired in June after 28 years at OHSU. “Nancy has always put the well-being of our patients as her top priority, and it is telling that even after 28 years, she continues to bring wisdom, compassion, skill and humor to her work each day,” said Susan Hedlund, LCSW, OSW-C., director of Patient & Family Support Services.

Sara A. Courtneidge, Ph.D. (Lena Hyde Photography)

Courtneidge honored as AACR fellow: Knight Cancer scientist Sara A. Courtneidge, Ph.D., is among the 25 newly elected fellows of the American Association for Cancer Research Academy, which cited her contributions to the understanding of oncogenic transformation. Fellows of the AACR Academy give advice and counsel on science policy. AACR noted her discovery that RSV v-Src transforming protein and c-Src are plasma membrane-associated, defining the activation mechanism of the c-Src tyrosine kinase; her discovery that c-Src is involved in polyomavirus transformation, which revolutionized the DNA tumor virus field; and her identifying Tks4 and Tks5 adaptor proteins as Src substrates that trigger invadopodia formation and protease secretion essential for tumor cell invasion.

National awards for OHSU surgeon’s cancer immune therapy research: Surgeon and cancer researcher Robert Eil, M.D., is exploring pathways to engineer the anti-tumor function of T cells. He is one of three researchers across the U.S. awarded Transformative Cancer Research Grants from the AACR-MPM Oncology Charitable Foundation. And he is one is one of seven early-career scientists across the nation selected for a career development award from the Pancreatic Cancer Action Network.

Science of the Patient award for two OHSU physician-scientists: Daniel Marks, M.D., Ph.D., and Aaron Grossberg, M.D., Ph.D., are among the first recipients of the new Science of the Patient Award from AACR and The Mark Foundation for Cancer Research. The three-year, $750,000 award will support their research on the wasting syndrome cachexia in pancreatic cancer. 

Prostate Cancer Foundation funds early-career biologist at OHSU: Amy Moran, Ph.D., received the foundation’s Young Investigator Award for her research on the role of hormones and immune cells in the most common cancer in men. Her project aims to reveal how androgens and androgen receptor activity regulate T cell function and immunotherapy resistance, which could point to new therapeutic approaches to reduce hormone-mediated immune suppression.

Defense Department funds CEDAR scientist: Thuy Ngo, Ph.D., is working to identify cell-free RNA biomarkers for the development of reliable blood tests for early diagnosis and treatment monitoring of liver cirrhosis and cancer. She has received a Peer Reviewed Cancer Research Program Idea Award from the military’s Office of the Congressionally Directed Medical Research Programs.

Career development award for breast cancer researcher: Joshua Saldivar, Ph.D., a CEDAR scientist and assistant professor of medicine, received the Breast Cancer Research Foundation-AACR Translational Research Career Development Award to Promote Diversity and Inclusion. The two-year, $150,000 grant is supporting Saldivar’s research on oncogenic ATR signaling during MYC-induced reprogramming in breast cancer.

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