Advancing Cancer Research and Treatment

Researchers affiliated with Siteman Cancer Center and/or Washington University School of Medicine in St. Louis have pioneered important advances in cancer research, prevention, education and treatment. Highlights and ongoing studies include these projects:

2017 — CAR-T cell therapy and using Zika virus to fight brain cancer

In a clinical trial at Siteman, at least 16 of 20 people who received a new treatment called CAR-T cell therapy saw their cancers disappear after treatment. The patients had previously failed standard therapies. CAR T-cell therapy, which uses a patient’s own immune system to attack cancer cells, is currently awaiting federal approval.

While Zika virus causes devastating damage to the brains of developing fetuses, it one day may be an effective treatment for glioblastoma, a deadly form of brain cancer. Joint research from Washington University School of Medicine and the University of California San Diego School of Medicine shows that the virus kills brain cancer stem cells, the kind of cells most resistant to standard treatments.

2016 — Chemotherapy for brain tumors

Using a laser probe, neurosurgeons open the brain’s protective cover, enabling them to deliver chemotherapy drugs to patients with glioblastoma – the most common and aggressive type of brain cancer. The patients underwent minimally invasive laser surgery to treat a recurrence of their tumors. Heat from the laser is known to kill brain tumor cells but, unexpectedly, the researchers found that the technology can penetrate the blood-brain barrier, keeping it open for four to six weeks and providing a therapeutic window of opportunity to deliver chemotherapy drugs.

2015 — Melanoma vaccine and urine test for kidney cancer

Personalized melanoma vaccines can be used to marshal a powerful immune response against unique mutations in patients’ tumors, according to early data in a first-in-people clinical trial. The new approach merges cancer genomics with cancer immunotherapy. Earlier attempts at vaccines have focused on targeting normal proteins commonly expressed at high levels in particular cancers. Those same proteins also are found in healthy cells, making it difficult to stimulate a potent immune response.

Researchers develop a noninvasive method to screen for kidney cancer that involves measuring the presence of proteins in the urine. The scientists found that the protein biomarkers are more than 95 percent accurate in identifying early-stage kidney cancers. In addition, there were no false positives caused by non-cancerous kidney disease.

2014 — Breast cancer, lung cancer and intraoperative cancer imaging

A breast cancer vaccine developed at Washington University School of Medicine is safe in patients with metastatic breast cancer, results of an early clinical trial indicate. Preliminary evidence also suggests that the vaccine primed the patients’ immune systems to attack tumor cells and helped slow the cancer’s progression.

A study involving lung cancer patients shows that current approaches to genome analysis systematically miss detecting a certain type of complex mutation in tumors. Further, a significant percentage of these complex mutations are found in well-known cancer genes that could be targeted by existing drugs, potentially expanding the number of cancer patients who may benefit.

Goggles developed at Washington University School of Medicine help surgeons visualize cancer cells, which glow blue when viewed through the eyewear. The goggles system, which incorporates custom video technology, a head-mounted display and a targeted molecular agent that attaches to cancer cells, helps to ensure that no stray tumor cells are left behind during surgery.

2013 — Endometrial cancer and leukemia

In separate studies, researchers at Washington University School of Medicine and The McDonnell Genome Institute help identify major genetic mutations that promote endometrial cancer and acute myeloid leukemia. The research, part of The Cancer Genome Atlas project, provides new information that could change treatments for patients and aid drug development.

2012 — Leukemia, breast cancer research and cancer prevention

Siteman leukemia doctor Lukas Wartman, MD, who was diagnosed with the disease himself, goes into remission for an unprecedented third time after Timothy Ley, MD, and his colleagues at The Genome Institute sequenced Wartman’s cancerous and normal genes. Researchers also analyzed his RNA. By doing so, his treatment team, which includes John DiPersio, MD, PhD, deputy director of Siteman, discovered that a normal gene might be contributing to the growth of Wartman’s cancer by producing mass amounts of a certain protein. They found that a drug used to treat a type of kidney cancer was able to inhibit the gene.

Scientists use whole genome sequencing to compare differences between the DNA of breast cancer tumors and healthy cells in 46 women. While revealing the complexity of the disease, the analysis suggests routes to personalized medicine that may have a greater probability of healing patients.

Building on his research for the Nurses Health Study and Growing Up Today Study, Graham Colditz, MD, DrPH, continues to examine links between cancer and alcohol use, diet, exercise and other factors and what individuals and communities can do to reduce disease risk. In a 2012 paper, Colditz argues that half of all cancer cases can be prevented, thereby saving more than 280,000 people in 2011, and that individuals, medical and health experts, government officials and others must start taking already known steps to reduce cancer’s impact.

2011 — Blood-related cancers

Siteman completes its 5,000th hematopoietic stem cell transplantation, a common therapy for patients with blood-related cancers such as leukemia, lymphoma, and multiple myeloma or another blood-related cancer.

2010 — Pediatric cancers

Washington University School of Medicine and St. Jude Children’s Research Hospital announce their joint Pediatric Cancer Genome Project to identify the genetic changes that give rise to some of the world’s deadliest childhood cancers. The team plans to decode the genomes of more than 600 childhood cancer patients who have contributed tumor samples.

2008 — Genetic sequencing

For the first time, scientists decode all the genes of a cancer patient and find a suite of mutations that might have caused the disease or aided its progression. Timothy Ley, MD, Elaine Mardis, PhD, Richard K. Wilson, PhD, and their colleagues at The McDonnell Genome Institute say the finding could lead to new therapies and could help doctors make better choices among existing treatments, based on a more detailed genetic picture of each patient’s cancer. Though the research involved acute myelogenous leukemia (AML), the same techniques can also be used to study other cancers.

2007 — Nanotechnology and radiation therapy

Gregory Lanza, MD, Ph.D., Samuel Wickline, MD, and researchers in their labs announce the development of nanoparticles, significantly smaller than the width of a human hair, aimed at attacking cancer by locating and “latching on” to tumors. Used in conjunction with magnetic resonance imaging, the nanoparticles could help physicians monitor cancerous tissue and deliver medicine directly to the tumor, not to the rest of the body.
Researchers led by Daniel Low, MD, and Parag Parikh, MD, develop a machine called the 4D Phantom that follows a patient’s complex breathing pattern to deliver radiation therapy to tumors that move, such as those in the lung.

2006 — Photoacoustic imaging

Lihong Wang, PhD, announces his work on photoacoustic imaging, a new technique that uses light and sound to create detailed, color pictures of tumors and organs. The noninvasive imaging technique, which can be performed without the dangers of radiation exposure associated with X-ray and CT scans, also may help doctors detect cancer earlier than ever before, its developers say.

2003 — Breast cancer

Thalachallour Mohanakumar, PhD, and other researchers at Siteman develop and test on mice a prototype vaccine that causes cancerous tumors to stop growing, then to shrink. The vaccine, which is being developed to fight breast cancer in humans, helps the immune system target a protein found in 80 percent of breast tumors.

2001 — Imaging and the immune system’s role in controlling cancer

Research led by Joanne Mortimer, MD, shows that positron emission tomography (PET) scans can often identify within two weeks which women with advanced breast cancer are likely to respond to hormone therapy, a gentler alternative to chemotherapy that is usually just as effective.

Robert D. Schreiber, PhD, and colleagues publish the first evidence that the immune system plays a role in controlling cancer, a process called immunosurveillance. In 2007, they find in mice that some cancers are kept in a state of “equilibrium,” which leads them to suggest that one day immunotherapy may convert cancer into a chronic but controllable disease.
Molecular oncologist Howard McLeod announces research on a genetic mutation that affects how well patients will respond to chemotherapy. The findings may make possible a blood test that would determine what dose, or even which drugs, would be most effective for each patient.

1998 — Biopsies

Ralph G. Dacey Jr., MD, performs the world’s first magnetic stereotactic surgery to biopsy a human brain tumor using an indirect route to the tumor. The route is designed to avoid regions that would normally be entered when a surgeon manually inserts a surgical tool straight at a site. The investigational computerized system allows surgeons to carefully manipulate surgical tools inside the brain through the use of a catheter driven by precisely controlled magnetic fields.

1994 — Genetic screening test for thyroid cancer

Led in part by Helen Donis-Keller, PhD, researchers for the first time develop genetic screening tests that detect a rare, lethal form of thyroid cancer in the preclinical state, permitting early treatment in children predisposed to the disease. It was the first surgical prevention of cancer based on genetic test results.

1979 — Bone marrow transplants

As part of a clinical trial, leukemia patients at Washington University in St. Louis and four other medical centers receive transplants of their healthy bone marrow cells to determine how effective the procedure is in conjunction with chemotherapy and radiation treatment. The new technique would later be called autologous hematopoietic stem cell transplantation.

Mid-1970s — Imaging

Michel Ter-Pogossian, PhD, leads the research that will turn the PET scanner from an intriguing concept to a medical imaging technique used by hospitals and laboratories everywhere to scan the working brain.

1954 — Growth factors and cancer

Rita Levi-Montalcini, PhD, and Stanley Cohen, PhD, isolate for the first time nerve growth factor, a potent substance that promotes nerve cell growth. The discovery later leads to insights into cancer and birth defects, and in 1986 the two are awarded a Nobel Prize for their work.

1946 — Radiocarbon in cancer research

For the first time, the United States Department of War releases carbon-14 isotopes to a civilian entity, Siteman’s predecessor institutions, Barnard Free Skin and Cancer Hospital (founded in 1905) and the Mallinckrodt Institute of Radiology (founded in 1923), where they are used in cancer studies.

1941 — Cyclotron

At the Mallinckrodt Institute of Radiology, construction begins on the first cyclotron devoted to medical and biological research.

1933 — Lung cancer surgery and the disease’s link to smoking

Evarts Ambrose Graham, MD, becomes the first surgeon to cure a human case of lung cancer by removing an entire lung during a procedure known as pneumonectomy. In 1950, he and Ernst Wynder, MD, publish the results of the first large-scale research on smoking, linking prolonged cigarette use to lung cancer.