Fifty years later, the OSUCCC – James remains focused on creating a cancer-free world. Here are a few of the program’s milestones and research highlights of the past half century.
1976
In April, the NCI designated Ohio State as a comprehensive cancer center (OSUCCC) — one of only 18 at the time — with David Yohn, PhD, as the first director. Yohn guided the OSUCCC through its early years and helped it start rising toward national prominence.
1980
Richard Olsen, DVM, PhD, led an OSUCCC team in veterinary pathobiology — including Larry Mathes, PhD — that discovered and developed a vaccine for feline leukemia, helping to protect cats from their No. 1 killer.
During the 1980s, Bertha Bouroncle, MD, Eric Kraut, MD, Michael Grever, MD, and colleagues developed the drug pentostatin for patients with hairy cell leukemia (HCL), a rare chronic leukemia that Bouroncle had identified in 1958. They showed that pentostatin induced over 90% complete remission in HCL patients. It became a standard therapy and changed the natural history of HCL from incurable to a disease for which patients regularly achieve remission.
1984
The university broke ground for a new freestanding cancer hospital that would become the adult patient care component of the OSUCCC.
1987
During a ceremony at which the cornerstone was set, then-Ohio State University president Edward Jennings announced that the hospital would be named for Arthur G. James, MD, a surgical oncologist who had spent nearly 40 years leading the charge for a cancer hospital in central Ohio.
1988
David Schuller, MD, a surgical oncologist and researcher in the Department of Otolaryngology Head and Neck Surgery, was named as director of The James (two years before it opened) and also of the OSUCCC. His tenure saw enormous growth in the OSUCCC – James’ ability to translate cancer research to innovative clinical care.
1990
The original James Cancer Hospital and Research Institute opened on July 9, 1990. Arthur G. James, MD, accompanied the first patient to be wheeled into the new facility from the adjoining Ohio State University Hospitals. Dr. James would retire from seeing patients in this same year, but he had an office at the hospital and maintained an everyday presence in an emeritus role until 1996. He died in 2001.
1995
The OSUCCC – James, under the leadership of David Schuller, MD, played a primary role in a multi-institutional phase III clinical trial demonstrating that chemotherapy plus radiation therapy improved survival of patients with advanced head and neck cancer compared with then-standard treatment of radiation therapy alone. This trial changed the standard of care for this disease.
1997
A new era in cancer research began at Ohio State with the recruitment of internationally renowned medical scientists Albert de la Chapelle, MD, PhD, Clara D. Bloomfield, MD, and Michael A. Caligiuri, MD. Bloomfield became director of the OSUCCC and deputy director of The James; de la Chapelle founded and directed the human cancer genetics program; and Caligiuri became associate director for clinical research at the OSUCCC. David Schuller, MD, remained as director of The James and became deputy director of the OSUCCC.
1998
The OSUCCC – James contributed to a landmark national study, the Breast Cancer Prevention Trial, which over the past six years had shown a 45% reduction in breast cancer cases among women at high risk for the disease who took the drug tamoxifen vs. placebo. William Farrar, MD, and David Schuller, MD, discussed the breakthrough at a press conference in The James Lobby. Tamoxifen became the first drug known to prevent rather than just treat breast cancer.
An international team led by Clara D. Bloomfield, MD, and Michael A. Caligiuri, MD, discovered a genetic marker for a novel mechanism of leukemogenesis that they called partial tandem duplication of the MLL oncogene. This was the first molecular marker discovered for patients with acute myeloid leukemia (AML) who have normal cytogenetics.
1999
Community leader Richard J. Solove, a longtime friend of Dr. James and supporter of the cancer program at Ohio State, donated $20 million to the OSUCCC – James Threshold of Discovery campaign for human cancer genetics research. In honor of this donation, the hospital was renamed the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.
2000
OSUCCC – James researcher Christoph Plass, PhD, led an international team that discovered and described the non-random and tumor-type specific nature of DNA promoter methylation in cancer. This was the first time DNA methylation had been examined in human cancer on so large a scale and with comparisons of so many tumor types.
2001
An OSUCCC – James team including Michael Ostrowski, PhD, Gustavo Leone, PhD, and Charis Eng, MD, PhD, presented one of the first microenvironment-based genetic models of the multi-step process leading to breast cancer. The model was based on their discovery that mutations in stromal cells (which surround or connect to tumors) are linked to cancer formation. They called the model “paradigm-shifting” because, previously, mutations leading to breast cancer were thought to occur only in epithelial cells, which line or cover organs.
The World Health Organization (WHO) classification of hematologic malignancies for the first time incorporated genetic studies rather than just morphology — particularly in AML— based in large part on the work of a WHO clinical advisory committee chaired by OSUCCC director Clara D. Bloomfield, MD. Under her leadership, the WHO classification for AML was further revised over the years based on molecular studies at Ohio State and other institutions.
2002
Pierluigi Porcu, MD, and Michael A. Caligiuri, MD, developed a therapy yielding the best reported survival to date for patients with post-transplant lymphoproliferative disorders (PTLD), an often lethal form of lymphoma associated with the Epstein-Barr virus. Of 11 patients on the therapy, 10 were alive nearly three years later with no sign of disease.
In the early 2000s, John C. Byrd, MD, was the national study leader for clinical trials in which rituximab became the first modern therapy to show significant improvement in overall survival for patients with chronic lymphocytic leukemia (CLL). Researchers found that combining rituximab with the standard chemotherapy drug fludarabine increased progression-free survival by 22% and overall survival by 12% compared with fludarabine alone.
2003
Clara D. Bloomfield, MD, stepped down as director of the OSUCCC and deputy director of The James to focus more fully on her pioneering research in adult leukemia and lymphoma. Michael A. Caligiuri, MD, succeeded her in both roles. David Schuller, MD, remained as executive director of The James and deputy director of the OSUCCC; Bloomfield became an Ohio State University cancer scholar and senior adviser to the OSUCCC – James.
Researchers led by Clara D. Bloomfield, MD, and Albert de la Chapelle, MD, PhD, reported that overexpression of a gene called BAALC, which they and others at Ohio State had co-discovered, is linked to poor response to therapy and shorter survival for patients with AML. Researchers could thus identify a new subset of AML patients who previously were classified as standard risk but who actually are more likely not to respond well to standard treatments.
William Carson, MD, led a research team that demonstrated in laboratory studies and clinical trials the effectiveness of combining the drug Herceptin with a cytokine called interleukin-12 (IL-12) to boost the immune system’s ability to fight breast cancers that overexpress the HER-2 protein.
2004
The first findings were reported from a long-term Ohio State study called the Stress and Immunity Breast Cancer Project led by Barbara Andersen, PhD, who started it in 1994 as a randomized clinical trial involving 227 women with stage II and III breast cancer. Findings indicated that a psychological counseling intervention for these patients can not only lower stress but also lead to healthier diets, reduced smoking and a stronger immune system.
2005
Scientists at the OSUCCC – James led the way in defining the role that microRNA may play in carcinogenesis. Carlo Croce, MD, and colleagues reported their discovery of how microRNA works in breast cancer and said the microRNA signature in this disease is linked to biological features that doctors may use for diagnosis and treatment.
Studies led by Albert de la Chapelle, MD, PhD, and Heather Hampel, MS, LGC, in 2005 and 2008 showed that one in 35 people with colon cancer also have Lynch syndrome (LS), an inherited condition that predisposes to colorectal, endometrial, ovarian and other cancers. The researchers recommended screening all newly diagnosed colon cancer patients for LS.
Since 2005, OSUCCC – James researchers have worked with scientists, medical professionals and policy experts from eight colleges at Ohio State in the Center for Advanced Functional Foods Research and Entrepreneurship (CAFFRE). This collaboration has resulted in more than $19 million in nationally sponsored projects and over 300 publications on food and health. Led by director Yael Vodovotz, PhD, and associate director Steven Clinton, MD, PhD, CAFFRE has commercialized several products, including soy-tomato juice, soy-almond bread and black raspberry confections — functional foods with anticancer properties that enhance human health.
2006
An international study led by OSUCCC – James researchers Christoph Plass, PhD, and Albert de la Chapelle, MD, PhD, discovered the first inherited gene mutation that increases risk for CLL. The mutation is in the DAPK1 gene.
A team led by Michael A. Caligiuri, MD, discovered the site and stages of development for natural killer (NK) cells, the last major set of human immune cells to be biologically characterized. The findings opened doors to manipulating the human immune system, possibly leading to new therapies for cancer, infection and immune deficiencies.
A study led by John C. Byrd, MD, revealed that a new strain of mouse offered the first real animal model for CLL. The TCL-1 transgenic mouse, originally engineered by Ohio State researcher Carlo Croce, MD, develops a malignancy that mimics CLL.
2007
A team led by David Schuller, MD, reported that three phase II trials at the OSUCCC – James over the past 12 years had shown that “intensification therapy” — a complex regimen of surgery, radiation and chemotherapy developed at Ohio State in the 1990s — is a difficult but tolerable treatment that yields good overall survival rates for patients with advanced head and neck cancers.
2008
The cancer program’s research and clinical components were consolidated into one leadership position held by Michael A. Caligiuri, MD, who succeeded David Schuller, MD, as CEO of The James while retaining his post as director of the OSUCCC. Schuller was appointed vice president for medical center expansion and outreach.
2009
A study at the OSUCCC – James indicated that some older AML patients (60 or above) whose cancer cells have mutations in the NPM1 gene respond better to therapy and experience longer survival. Study leader Clara D. Bloomfield, MD, said researchers knew mutations in this gene signaled a favorable prognosis for younger AML patients, but this study’s findings indicated the same is true for older patients, suggesting they should be offered stronger therapy.
2011
A team of surgeons removed the left leg, hip and pelvis of a cancer patient and used the healthy bones from his amputated leg to rebuild the connection between his spine and remaining right pelvis to support a high-tech prosthetic leg. It was the first time the procedure had been performed in the United States, according to Joel Mayerson, MD, an orthopedic oncologist who worked with a team that included neurosurgeon Ehud Mendel, MD, and plastic surgeon Michael Miller, MD. Their work was voted “Reconstructive Surgery Case of the Year” by the American Society of Reconstructive Microsurgeons.
A study at the OSUCCC – James showed that the loss of the NFKBIA gene promotes the growth of glioblastoma multiforme, the most common and deadly form of brain cancer. Published in the New England Journal of Medicine, the study suggested that therapies to stabilize this gene may improve survival for certain patients. Senior co-author Arnab Chakravarti, MD, said investigators showed the gene may be an independent predictor of survival in some patients.
2012
A study led by Clara D. Bloomfield, MD, and published in the journal Blood found that older people with AML and normal-looking chromosomes in their cancer cells have a higher risk of recurrence if they have mutations in the ASXL1 gene. The study was the first to investigate the influence of these mutations on prognosis in patents with cytogenetically normal AML and in conjunction with other prognostic gene mutations.
2013
Clinical studies published in the New England Journal of Medicine suggested that the drug ibrutinib shows strong potential as a safe, effective, targeted treatment for patients with chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL). The studies, co-led by researchers at the OSUCCC – James and MD Anderson Cancer Center, resulted in FDA approval of ibrutinib for treating relapsed MCL. The CLL study leader was John C. Byrd, MD; the MCL study leader was Kristie Blum, MD.
An OSUCCC – James study showed that women who wait more than 60 days to begin treatment for advanced breast cancer face a significantly higher risk of dying than women who start therapy shortly after diagnosis. A delay of more than 60 days among women with late-stage disease was associated with an 85% higher risk of breast cancer-related death. Electra Paskett, PhD, MSPH, was senior author of this study, published in the Journal of Clinical Oncology.
2014
The FDA expanded the approved use of the drug ibrutinib (Imbruvica®) to treat certain patients with CLL. Ibrutinib was the first drug designed to target a protein that is essential for CLL cell survival and proliferation. Much of the clinical and basic-science research that led to FDA approval was performed by OSUCCC – James scientists, including John C. Byrd, MD, Amy Johnson, PhD, Jason Dubovsky, PhD, Jeffrey Jones, MD, MPH, Joseph Flynn, DO, MPH, Jennifer Woyach, MD, Kami Maddocks, MD, and Kristie Blum, MD.
In December, the new James Cancer Hospital and Solove Research Institute opened to replace the original James that had opened in 1990. With 1.1 million square feet and 356 beds, the new James is the third-largest cancer hospital in the United States — a transformational facility that integrates cancer research and clinical care more closely than ever.
2015
A study published in the New England Journal of Medicine showed that the drug acalabrutinib promotes high and durable response rates in patients with CLL while producing minimal side effects. The drug is a second-generation Bruton tyrosine kinase (BTK) inhibitor. Preclinical and clinical efforts with acalabrutinib were led by John C. Byrd, MD, and Amy Johnson, PhD.
The American Cancer Society featured a study by OSUCCC – James researchers as one of “10 Key Breakthroughs and Insights for 2015.” Led by Deliang Guo, PhD, and published in the journal Cancer Cell, the study identified a pathway used by cancer cells to make lipids (fats) by integrating oncogenic signaling, fuel availability and lipid synthesis to support cell division and rapid tumor growth. They found a molecule in that pathway that, if blocked, could cripple lipid production by cancer cells and slow tumor growth.
2016
A study conducted at Nationwide Children’s Hospital (NCH) and led by Timothy Cripe, MD, PhD, of NCH and the OSUCCC – James, found that a new chemotherapy is effective against both pediatric and adult cancers, and that it allowed other chemotherapies to more readily reach their targets. Published in the journal Pharmaceutical Research, the study described a novel class of anticancer amphiphilic amines (RCn).
The OSUCCC – James assumed a lead role in a “Beat AML” clinical trial sponsored by the Leukemia & Lymphoma Society. The ongoing trial represents collaboration among leukemia researchers and medical centers, non-profit corporations, pharmaceutical companies and a genomics information company to advance treatment for AML.
2017
A few weeks after the U.S. FDA permitted marketing of the first whole slide imaging (WSI) system for review and interpretation of digital surgical pathology slides from biopsied tissue, the OSUCCC – James initiated a comprehensive Digital Pathology Program to fully digitize anatomical pathology services using WSI technology under the leadership of director Anil Parwani, MD, PhD, MBA.
The FDA approved a breakthrough cancer treatment called chimeric antigen receptor T-cell (CAR T-cell) therapy for use in adults with advanced lymphoma and for treating a rare type of treatment-resistant childhood leukemia. Samantha Jaglowski, MD, MPH, tested the therapy in clinical trials at Ohio State.
OSUCCC director and James CEO Michael A. Caligiuri, MD, stepped down to embark on a new career opportunity in California. Surgical oncologist Raphael E. Pollock, MD, PhD, FACS, became director of the OSUCCC; surgical oncologist William B. Farrar, MD, became interim (and later permanent) CEO of The James.
2018
A study by researchers at the OSUCCC – James and Ohio State’s College of Pharmacy showed that attaching antibody-like RNA nanoparticles to microvesicles can deliver RNA therapeutics specifically to cancer cells. Researchers led by Peixuan Guo, PhD, used RNA nanotechnology to apply the RNA nanoparticles and control their orientation to produce microscopic, therapy-loaded extracellular vesicles that targeted three types of cancer in animal models.
2019
OSUCCC – James researchers reported the first evidence of biological changes correlated with e-cig use in never-smokers in the journal Cancer Prevention Research. Peter Shields, MD, was senior author, and Min-Ae Song, PhD, was first author of the study, which was one of the most highly cited articles published in 2019 in this journal.
A pledge of $102,265,000 in funds from Pelotonia supported the establishment of the Pelotonia Institute for Immuno-Oncology (PIIO), a comprehensive bench-to-bedside research initiative focused on harnessing the body’s immune system to fight cancer at all levels, from prevention to treatment to survivorship. Renowned immunologist Zihai Li, MD, PhD, is the founding director.
The FDA approved the use of acalabrutinib for first-line therapy in chronic lymphocytic leukemia (CLL) and small cell lymphoma (SCL). This was the first full approval of the targeted drug therapy, which was developed and tested at the OSUCCC – James with Acerta Pharma. The basic science research, initial phase I clinical trial, and numerous sequential phase II and III trials that led to FDA approval were performed by Ohio State researchers led by John C. Byrd, MD, and colleagues, including William Kisseberth, DVM, PhD, and Jennifer Woyach, MD.
2020
A study led by researchers at the OSUCCC – James identified a protein within certain immune cells that is required for optimal immune responses to cancer. The findings also suggest the protein, called PCBP1, might be useful for predicting which cancer patients are less likely to respond to immune checkpoint blockade therapy. Zihai Li, MD, PhD, was principal investigator; Ephraim Abrokwa Ansa-Addo, PhD, was first author.
These highlights are only a few of the many achievements by experts in Ohio State’s cancer program over the past 50 years. Read a longer review of highlights in Half a Century of Cancer Science at Ohio State at cancer.osu.edu/halfcentury.