The National Foundation for Cancer Research funds leading scientists in the cutting-edge fields of immune-oncology, angiogenesis, metastasis, targeted cancer therapies, bioinformatics and others. These initiatives continue to have the highest potential to positively impact the cancer research field and bring precision medicine to patients with all types of cancer.
Wayne Marasco, M.D., Ph.D.
NFCR Center for Therapeutic Antibody Engineering, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Research Focus: Monoclonal Antibody Engineering
One promising approach to treating cancer is monoclonal antibody therapy — a type of immunotherapy in which specialized proteins called antibodies attach to specific structures on the surface of cancer cells, then alert the patient’s own immune cells to attack the cancer. Designing the antibodies for this type of therapy is a challenging feat of molecular engineering — one ably met by Dr. Marasco and his team at the NFCR Center for Therapeutic Antibody Engineering. Dr. Marasco has had great success developing antibodies that attach to carbonic anhydrase IX (CAIX), an important protein expressed in renal cell carcinoma — the most common type of kidney cancer — and recently reported in cancers of the mouth and lungs as well. For Dr. Marasco, the ultimate goal is always to translate his findings into new drugs for patients.
Paul Fisher M.Ph., Ph.D.
Virginia Commonwealth University School of Medicine, Richmond, VA
Research Focus: Cancer Terminator Viruses
Dr. Fisher has developed a new therapeutic approach to cancer therapy, which he calls a Cancer Terminator Virus. The agent, which is a virus genetically reprogrammed to infect and destroy tumor cells while leaving normal cells alone, is used to treat both early stage and metastatic prostate cancer, and recently expanded to treatment of pancreatic cancer as well. Dr. Fisher has also developed the first sensitive and specific imaging agent for bone metastases — the number one cause of death for patients with prostate cancer. The new molecular imaging technique detects cells that express a gene called AEG-1, which was originally discovered by Dr. Fisher. It is expressed at high levels in all cancer types investigated so far, with limited expression in normal tissue. This represents a great improvement over current clinical imaging techniques, and could lead to earlier detection and treatment of metastases — not only originating from prostate cancer, but from several other cancer types as well.
Harold F. Dvorak, M.D.
Beth Israel Deaconess Medical Center, Boston, MA
Research Focus: Tumor Angiogenesis and Anti-Vascular Therapy
Dr. Dvorak is a long-time NFCR Fellow, and winner of the inaugural Albert Szent-Györgyi Prize for his discovery of VEGF (vascular endothelial growth factor). VEGF plays a central role in angiogenesis, the process by which tumors recruit blood vessels to supply the nutrients they need to grow and survive. Dr. Dvorak’s research has contributed immensely to scientists’ understanding of this process, and led to the development of a new class of anti-angiogenic therapies that target tumor blood vessels. His latest work is focused on tumor’s “feeding arteries” and “draining veins” — the larger vessels that carry blood into and out of tumors — with the goal of determining how they form and whether they can be targeted to cut off the tumor blood supply. This novel approach, which is analogous to cutting off the water supply for the entire street, rather than turning off all the faucets in the house, has great potential for more effectively treating many types of cancer.
Rakesh K. Jain, Ph.D.
Massachusetts General Hospital, Boston, MA
Research Focus: Attacking Brain Tumor Blood Vessels
Dr. Jain is a leader in the field of anti-angiogenic therapy. His seminal research demonstrated that anti-angiogenic therapy works by normalizing the abnormal, leaky vessels that usually surround and penetrate tumors. This process both improves delivery of chemotherapy drugs and increases the oxygen content of cancer cells, making radiation therapy more effective. Dr. Jain is now focused on the role of angiogenesis in glioblastoma multiforme (GBM). By identifying the characteristics that confer resistance to anti-angiogenic therapy in GBM patients, Dr. Jain’s research is helping doctors to better tailor the use of anti-angiogenic therapies for GBM patients in the clinics. Additionally, the molecular resistance pathways that Dr. Jain and his team identify will direct the development of novel agents targeting these pathways, which could extend the benefits of anti-angiogenic therapy for patients.
Danny Welch, Ph.D.
NFCR Center for Metastasis Research
The University of Kansas Cancer Center, Kansas City, KS
Research Focus: Cancer Metastasis
Since its inception, Dr. Welch has directed the NFCR Center for Metastasis Research in its investigations of cancer biology related to metastasis — the process responsible for the vast majority of patient deaths across all types of cancer. Dr. Welch and his team have identified genes regulating metastasis, particularly metastasis suppressors; investigated the interactions between metastases and their surrounding tissues, especially for bone metastases; and are now working to translate their findings into clinical practice. Through research, they identified genetic changes that predict whether patients will or will not develop metastasis. At least some of these changes occur in mitochondria — where cells convert nutrients into energy. These results could determine that a simple blood draw and analysis of mitochondrial DNA, which is present in every cell and which is small enough to be rapidly analyzed, could be used to help doctors guide their strategy to treat patients.
Daniel A. Haber, M.D., Ph.D.
Massachusetts General Hospital Cancer Center, Boston, MA
Research Focus: Circulating Tumor Cells
Dr. Haber and his team developed the CTC-iChip — an advanced micro-engineered device that is capable of capturing extremely rare circulating tumor cells (CTCs) from the blood. This device could dramatically improve treatment and diagnosis of many different types of metastatic cancer. Thanks to recent improvements in design, Dr. Haber is now able to use the CTC-iChip to investigate the ways in which cancer cells leave the primary tumor and invade into the bloodstream to spread and initiate metastasis. By testing the CTCs, they have discovered that some genes are specifically activated as cancer cells leave the tumor and enter blood circulation. He and his team are now learning about the properties of these genes to better understand how cancer cells spread through the blood, and whether targeting these genes could prevent metastasis.
OVERCOMING DRUG RESISTANCE
Susan Band Horwitz, Ph.D.
Albert Einstein College of Medicine, New York, NY
Research Focus: Natural Product-Derived Anti-cancer Drugs and Drug Resistance
Dr. Horwitz is a world-renowned cancer researcher, whose work has been instrumental in the development of a successful class of anti-cancer drugs called Microtubule- Stabilizing Agents (MSAs) — a class that includes Taxol®, a natural product-derived drug used extensively in the treatment of breast cancer and other types of cancer worldwide. Taxol is effective to many breast cancer patients, but some patients will become resistant to it. Dr. Horwitz is collaborating with other scientists to develop new drugs to overcome the drug resistance problem. The new drugs are hybrid molecules containing the active segments of Taxol and another drug called discodermolide. These hybrid molecules will have increased affinity to the cancer targets and reduced risk of drug resistance. Two candidate molecules have been identified and tested in a panel of breast cancer cell lines. The results were very promising, and the candidate molecules will be further tested to evaluate their efficacy and toxicity on more complex tumor models. With more positive results, the candidate molecules could move to the clinical trial stage.
Alice Shaw, M.D., Ph.D.
Massachusetts General Hospital, Boston, MA
Research Focus: Overcoming Drug Resistance
With the support of the Hillsberg Lung Cancer Translational Research Grant, an NFCR donor-advised fund, Dr. Shaw and her team have developed a platform to rapidly identify effective drug combinations for lung cancer patients whose tumors have stopped responding to targeted therapy. In their research, cells taken directly from patients’ tumors were grown in the laboratory and treated with a host of different drug combinations to find the ones that work — both attacking the cancer, and cutting off the “escape pathways” that can cause resistance. The approach has identified several effective drug combinations — including some that standard testing would not have predicted to work. With further refinements, this strategy might be used to select the optimal treatment for each individual patient, making precision medicine a reality for lung cancer patients — and for other types of cancer as well.
Jin Jen, M.D., Ph.D.
Mayo Clinic, Rochester, MN
Research Focus: Fighting Drug Resistance in ALK+ Lung Cancer
Dr. Jen and her team are developing a platform for fighting drug resistance in ALK-positive (ALK+) lung cancer. In an exciting project supported through NFCR’s Hillsberg Lung Cancer Translational Research Grant, Dr. Jen is performing advanced genomic analysis on tumor biopsies collected from ALK+ lung cancer patients whose cancer has recurred because of the drug resistance. She also established tumor models derived from the same patients’ biopsies. By integrating the genetic, clinical, and patient-specific tumor model data, Dr. Jen’s research will help doctors choose the best possible drug for each specific patient in the project.
Robert C. Bast, Jr., M.D.
MD Anderson Cancer Center, Houston, TX
Research Focus: Early Detection of Ovarian Cancer
Early detection is considered the most effective means to achieve a cure in ovarian cancer. The five-year survival rate is above 90% if ovarian cancer is found during the earliest stage; unfortunately, only 15% of cases are diagnosed at this stage. Dr. Bast is working to change that. Using a special imaging device called a Superconducting Quantum Interfering Device (SQUID), which promises to improve sensitivity by several orders of magnitude over existing techniques, such as CT, MRI and PET-CT. Dr. Bast and his colleagues are working to identify the best combination of biomarkers that can be used together to produce the most sensitive, ovarian-cancer-identifying signal possible. Using more specific and sensitive biomarkers in conjunction with SQUID technology could greatly increase early detection and diagnosis of ovarian tumors at a time that would offer the best opportunity for a cure.
James Basilion, Ph.D.
NFCR Center for Molecular Imaging
Case Western Reserve University, Cleveland, OH
Research Focus: Highly Sensitive Molecular Imaging for Early Detection of Cancers
Dr. Basilion and his team at the NFCR Center for Molecular Imaging are developing advanced new techniques that could change the way doctors look at cancer. Each tumor has a complex genetic signature, and a new molecular probe designed at the Center allows doctors to simultaneously visualize many different aspects of this signature in real-time — leading to better diagnoses and earlier detection of cancers. Dr. Basilion and scientists at the Center have also developed an imaging technique that could revolutionize cancer surgery, both for breast lumpectomy and skin cancer. The new technology consists of a light-emitting probe that binds to the cancers cells. It is many times more sensitive than existing probes and works within minutes, allowing surgeons to assess, in real time, whether the margins of their surgeries are cancer-free. This novel approach, which may soon advance to clinical trials, could dramatically reduce the re-excision rates (currently 20–60% for lumpectomy), and more importantly reduce or eliminate local recurrence due to “surgically missed” cancerous tissues.
Helmut Sies, M.D.
Heinrich-Heine-Universität, Düsseldorf, Germany
Research Focus: Nutrition and Cancer Prevention
Dr. Sies previously discovered that the antioxidant lycopene, a micronutrient found in tomatoes and other foods, has strong skin cancer prevention effects. Today, his research is focused on selenium (Se), a trace metal found in food sources such as certain nuts, seafood and organ meats, is essential for good health. There is epidemiological evidence that adequate intake of selenium is beneficial for human health and cancer prevention — especially colon cancer — and Dr. Sies is establishing the molecular basis for this effect. Key antioxidant enzymes called selenoproteins require selenium to repair oxidative damage. Dr. Sies discovered that not only are selenoproteins strongly decreased in colon cancer tumor cells, but they are strongly expressed by immune cells in the gut. Moreover, dietary selenium compounds were found to stimulate colon cells to produce selenoproteins, suggesting a potential mechanism for how selenium from ingested food supports immune health and cancer prevention.
PRECISION TREATMENTS | GENOMIC THERAPIES
W. K. Alfred Yung, M.D.
MD Anderson Cancer Center, Houston, TX
Research Focus: Identifying New Targets for GBM
To advance the search for new treatments for glioblastoma multiforme (GBM), Dr. Yung and his team are especially focused on drugs that target a gene called PI3K, a key factor in about 30% of GBM cases. His team developed a special panel of cell lines made from glioma stem cells (GSCs) collected from many GBM patients. The cell lines allow them to investigate patterns of resistance to P13K inhibitors. By establishing the molecular profile of these GSCs, the researchers can identify potential targets for new drug development. Dr. Yung’s team now reports that after treatment with P13K inhibitors, the molecular profile of GSCs changed and shows increased levels of Wee-1, a critical protein in controlling cell division and growth. Combining a P13K inhibitor with a Wee-1 inhibitor resulted in greater inhibition of cell growth and significantly, also induced the cancer cells into cell suicide. The two inhibitors used together also showed similar benefits in GBM complex tumor models. Continued success by Dr. Yung’s team in discovery of targets and design of rationale combination therapies may rapidly bring new treatments to the clinic.
Daniel Von Hoff, M.D. and Laurence Hurley, Ph.D.
NFCR Center for Targeted Cancer Therapies
Translational Genomics Research Institute, Phoenix, AZ
Research Focus: Targeted Therapeutics Development
At the NFCR Center for Targeted Cancer Therapies, Co-Directors Dr. Von Hoff and Dr. Hurley are pioneering new approaches to attack the so-called “undruggable” targets present in many tumors. They have had great success identifying multiple new compounds that selectively kill pancreatic cancer cells with mutations in the K-ras gene, and the leading compounds are currently being further developed for possible translation into the clinic. In addition, the Center is embarking on an entirely new approach to treating cancer, developing drugs that block newly-recognized genetic structures called “super enhancers.” These large clusters of DNA regulatory elements, which control expression of a host of genes — including the critical cancer gene c-Myc offer a great opportunity to disrupt the network of genes associated with cancers. This new approach may lead to great improvements in the treatment of pancreatic cancer, lymphoma, multiple myeloma, colorectal and other cancers.
Wei Zhang, Ph.D.
NFCR Center for Cancer Systems Informatics
Wake Forest Baptist Medical Center, Winston-Salem
(Formerly at MD Anderson Cancer Center, Houston, TX)
Research Focus: Cancer Genetics and Personalized Medicine
Molecular classification of patients into different subtypes based on genetic or epigenetic characteristics or biomarkers offers a great opportunity for personalized cancer treatment. Center researchers have the tools and the drive to interrogate and analyze large datasets of cancer from The Cancer Genome Atlas (TCGA). They identified mutations in the ADAMTS gene family in ovarian cancer cases which were significantly associated with an improved response to platinum-based chemotherapy and longer survival. They identified a new epigenetic biomarker for prognosis in GBM (glioblastoma multiforme) patients with multiple lesions. Cancer stem cell characteristics were identified in a subset of liver cancer patients who have a poor prognosis, a first step towards developing a system to classify this cancer on the basis of biomarkers. In these and other studies, this NFCR Center is making invaluable contributions to our understanding of the molecular and genomic events that underlie many cancer types, and ultimately improving patient care.
Joint Tumor Tissue Bank
Tianjin Cancer Institute and Hospital, Tianjin, China
Research Focus: Early Detection of Lung Cancer
Lung cancer is the most commonly diagnosed cancer worldwide, and accounts for 18% of cancer deaths. When diagnosed in early stages, however, the 5-year survival is greater than 50%, but is dismal when diagnosed at late stages. Better tools are needed to identify patients with lung cancer at early and potentially treatable stages.
Low dose, spiral CT scans for high risk populations are now recommended in the U.S. The cost of CT screening to the health care system is high; however, the follow up testing is invasive. Additional tools are necessary to select and target the population at highest risk for lung cancer.
Collaborations have been initiated in the Joint Tumor Tissue Bank in Tianjin to develop a blood test for early detection of lung cancer. The test will measure a panel of biomarkers comprising tumor antigens and autoantibodies for people who are 20-pack/year smokers over age 50 without obvious symptoms of lung cancer. If successful, the simple blood test could be a very powerful and inexpensive tool to detect lung cancer at an early stage in this high risk population. In the long run, this could save tens of thousands of lives.
Brian Leyland-Jones, M.D., Ph.D.
Director, Consortium for Clinical Diagnostics (CCDx)
Research Focus: Biomarker Profiling and Validation
Biomarkers are revolutionizing cancer therapies and diagnostics. There is a growing and urgent need for biomarker profiling and validation in cancer research today. The Consortium for Clinical Diagnostics (CCDx) is a partnership of scientists at research institutions and biopharmaceutical companies dedicated to facilitating genomic research and diagnostics. Led by Director Dr. Brian Leyland-Jones, CCDx provides centralized infrastructure and expertise in genomics and molecular imaging as well as translational medicine. The Consortium can identify and validate disease genes and genetic signatures, and allow for the development of medical response tests as well as new and improved diagnostic tests — especially in the area of cancer.
Curt Civin, M.D.
University of Maryland School of Medicine, Baltimore, MD
Research Focus: Advancing Artemisinins for AML Treatment
Leukemia is a great success story for cancer research — one in which Dr. Civin played an important role. His early work on bone marrow stem cell transplantation was partially responsible for the dramatic increase in 5-year survival for all types of leukemia over the past 20 years. Unfortunately, acute myeloid leukemia (AML) remains the deadliest form of leukemia. Dr. Civin discovered that artemisinins, a class drugs with low toxicity used to successfully treat malaria, are also effective in killing AML cancer cells. Through research, he identified ART-838, a specific artemisinin compound that shows remarkable preliminary effectiveness against leukemia cells and works well in combination with established anti-leukemia drugs. In addition, the compound can be given orally and stays active in the bloodstream for a long time, and doesn’t appear to harm normal bone marrow cells. ART-838 may prove to be an effective new treatment for AML patients.
Paul Schimmel, Ph.D.
The Scripps Research Institute, San Diego, CA
Research Focus: New Avenues for Cancer Treatment
A world-renowned biochemist, Dr. Schimmel has dedicated his 40-year career to understanding how the genetic information encoded in RNA gets translated into protein — the most fundamental chemical process for all living things. His work has led to the discovery of a major new way to relieve the adverse effects of cancer drugs that can harm other parts of the body, especially the blood supply. One key protein Dr. Schimmel has been investigating was found to restore platelet counts, offering hope for cancer patients with thrombocytopenia. In addition, Dr. Schimmel and his team discovered how resveratrol, as a natural ingredient found in foods including cacao and grape skins, works with another key protein to produce protective effects against cancer — a true breakthrough for cancer prevention. The mechanism could also be utilized to develop new treatments or chemoprevention agents.
Yung-Chi Cheng, Ph.D.
Yale University School of Medicine, New Haven, CT
Research Focus: Using Traditional Chinese Medicine to Treat Cancers
While the therapeutic effects of Traditional Chinese Medicine (TCM) have been documented anecdotally for centuries, they have been too often discounted by modern medicine as “alternative therapy” because there was little rigorous scientific proof of their effectiveness. Dr. Cheng’s laboratory is working to bring TCM into the mainstream of Western medicine. Their formulation of an ancient Chinese herbal formula, PHY906, is currently being evaluated in two separate Phase 2 clinical trials. In a trial treating colorectal cancer patients with the chemotherapy agent irinotecan (Camptosar®), PHY906 is an adjunct agent to reduce the chemotherapy-induced toxicity, especially diarrhea. A 2nd trial uses PHY906 as an adjunct agent to enhance the anti-cancer effects of the drug, Sorafenib, in the treatment of liver cancer patients. PHY906 could become one of the first FDA-approved oral herbal medicines for cancer treatment. Dr. Cheng and his team are also evaluating other herbal formulas from TCM, with the hope of developing a new class of anti-cancer drugs.