Beth Israel Deaconess Medical Center

Boston, Massachusetts
Chief of Pathology, Beth Israel Deaconess Medical Center
Mallinckrodt Distinguished Professor of Pathology, Harvard Medical School

Research

Harold F. Dvorak, M.D., discovered that tumor cells secrete a vascular endothelial growth factor (VEGF) and this seminal discovery provided the molecular basis for the field of angiogenesis (meaning “blood vessel formation”). Angiogenesis makes it possible for tumors to grow and spread, and Dr. Dvorak’s discovery helped pave the way for research on anti-angiogenesis treatments that can halt and even reverse tumor growth.

In 2004, the first VEGF-targeting anti-angiogenic drug Avastin® was approved by the FDA for the treatment of colorectal cancer, and, today, in addition to colorectal cancer, Avastin is approved for the treatment of non-small cell lung cancer, renal cell carcinoma, the aggressive brain cancer glioblastoma multiforme (GBM) and certain types of cervical and ovarian cancers. More than 280 clinical trials are currently investigating the use of Avastin in over 50 tumor types.

Dr. Dvorak’s recent research projects have led to the identification and characterization of at least six different kinds of blood vessels in tumors. While current anti-angiogenic therapies primarily act against only one of them, his research group has already discovered new therapeutic targets on the other five vessel types. They are aiming to improve the effectiveness of anti-angiogenic therapy by attacking the entire tumor environment, providing opportunities for new types of anti-cancer treatments.

Bio

Harold F. Dvorak, M.D. attended Princeton University and Harvard Medical School. He started his career with residency training in pathology at Massachusetts General Hospital (MGH) and spent two years as a post-doctorate at the National Institutes of Health. Dr. Dvorak worked as a staff pathologist at MGH for 16 years and then spent almost 30 years at Beth Israel Deaconess Medical Center.

Dr. Dvorak served on the faculty of Harvard Medical School starting in 1967 and, throughout his career, was a visiting professor at numerous national and international scientific conferences. In addition to his long-running fellowship with NFCR, he was a fellow of the American Association for the Advancement of Science and served as President of the American Society for Investigative Pathology.

Dr. Dvorak was the first winner of NFCR’s Szent-Györgyi Prize for Progress in Cancer Research in 2006 for his discovery of VEGF. He also won the 2002 Rous-Whipple award from the American Society for Investigative Pathology and the 2005 Grand Prix Lefoulon-Delalande from the Institut de France.

Related Content

NFCR Fellow’s Research Sheds Light on Mechanism for Blood Vessel Formation in Cancer

Almost all living things need oxygen to survive. In human cells, the key to staying healthy is the right balance of oxygen. NFCR fellow Xiang-Lei Yang a professor at Scripps Research Institute has spent much of her career exploring the processes by which tumors sprout new blood vessels when they are oxygen-starved, a process known as angiogenesis. Dr. Xiang-Lei Yang, and NFCR-funded scientist Dr. Paul Schimmel, are worldwide experts in aminoacyl-tRNA synthetases (aaRS). aaRS is a family of enzymes that catalyze the synthesis of proteins from tRNA. While aaRS’s are best known for their role in protein synthesis, Dr. Yang discovered that a particular aaRS, SerRS, also plays a role in inhibiting angiogenesis.   Prior angiogenesis research suggests that two genes — c-Myc and HIF-1 — are responsible for promoting blood vessel growth in healthy cells and tumors alike. As such, the turning on and transcription of these genes can promote tumor oxygenation and growth. In particular, c-Myc is one of the most important cancer-causing genes upregulated in many types of cancer. It also controls the gene for the production of VEGF, a blood vessel growth factor.   In addition to its role in protein synthesis, SerRS limits blood vessel growth by inhibiting the function of the c-Myc and HIF-1. In the study published in PLOS Biology (December 2020), Yang and her fellow researchers share the discovery that during hypoxia, or oxygen starvation, proteins known as ATM/ATR are activated. The ATM/ATR protein activation “silences” or inhibits SerRS and promotes the formation of new blood vessels. Additionally, in separate studies of mice and human breast tissue, the researchers were able to display that ATM/ATR activation had a blocking effect on SerRS and resulted in reduced tumor size.   In researching the role of ATM/ATR activation, and SerRS in breast cancer, Dr. Yang’s team found that the expression of SerRS is positively correlated with a greater rate of survival in breast cancer patients. Also, SerRS is significantly downregulated when metastasis, or cancer spread, occurs. Similar findings have been made in several other cancer types including brain, esophageal, kidney (clear cell), rectal, stomach, and thyroid cancers. These findings suggest that SerRS can inhibit the growth and metastasis of certain cancers and that ATM/ATR activation can counter that inhibition. These discoveries, funded in part by the National Foundation for Cancer Research, are core to our understanding of why and how tumors form new blood vessels and metastasize. As such, these discoveries may lead to novel therapeutic approaches that seek to limit ATM/ATR activation.   

New Brain Scan Technology Can Improve Tumor Removal

Any illness or disease that impacts the brain is highly complex. None more so than brain tumors, which affect over 20,000 Americans each year. While surgeons have become more advanced in the removal of brain tumors, experts continue to face extreme challenges in ensuring all cancerous tissues are removed during surgery. That is, until now.  A recent study found a high-intensity focused ultrasound 2.5 times more effective at identifying cancerous tissue than surgeons alone and significantly better than traditional ultrasound. The newly identified ultrasound cancer treatment technique is referred to as shear wave elastography.  Shear wave elastography measures the stiffness and stretch within the tissue, with vibrations moving faster through stiffer tissue. Brain tumors tend to be stiffer than normal brain tissue, allowing the new method to map suspicious areas of particular stiffness. In the study, researchers compared this high-intensity focused ultrasound to the standard ultrasound cancer treatment and a surgeon’s opinion regarding which tissues to remove.  The study used these three different techniques on a total of 26 patients. All of the techniques were compared with gold-standard MRI scans after the surgery – which while effective, are exceptionally time-consuming and expensive.  While the shear wave elastography ultrasound cancer treatment proved to be the most effective with 94% sensitivity (compared to 73% for the standard ultrasound tumor removal and 36% for the surgeon’s opinion), researchers concluded that the shear wave scans may yield more false positives than surgeons.  Ensuring all of a brain tumor is removed without damaging healthy tissue is a major challenge in brain surgery. This new type of scan can greatly increase a surgeon’s confidence that no cancer tissue is left behind in surgery.  The use of this unique ultrasound in cancer treatment makes a significant stride towards improving the health outlook for brain cancer patients. The National Foundation for Cancer Research (NFCR) is also providing new hope in the realm of brain cancer through its partnership with Global Coalition for Adaptive Research (GCAR). GCAR is a nonprofit organization comprised of some of the world’s foremost physicians, clinical researchers and investigators united in expediting the discovery and development of cures for patients with rare and deadly diseases. GCAR is the official sponsor of GBM AGILE, an adaptive platform trial for patients with glioblastoma (GBM) – the most common and deadliest of malignant primary brain tumors. The GBM AGILE has been developed with a revolutionary approach to defeating GBM, with the goal of enabling faster and more efficient testing of new agents and combination therapies, better identification of predictive and prognostic biomarkers and delivery of more effective treatments to all glioblastoma patients. GBM AGILE is an innovative approach for treating brain cancer, providing new hope where little existed before. NFCR continues to fund innovative researchers paving the way to finding new screening methods, treatments, and cures for all cancers, including brain cancer. To learn more about the progress that NFCR-funded scientists are making in the way of brain cancer, visit the NFCR Brain Cancer page.  Additional Reads You May Enjoy: “Pink Drink” to Aid Brain Tumor Treatment Treating Brain Cancer: What You Need to Know GBM AGILE – Changing the Way We Fight Brain Cancer Stay connected with us! […]

Phase II Clinical Trials May Be on the Way for Ovarian Cancer

Dubbed one of the notorious ‘silent killers’, ovarian cancer claims the lives of approximately 14,000 American women each year. Tragically, all women are at risk and early detection and sustainable treatment have proved to be difficult. However, a recent study provides new hope in the realm of ovarian cancer treatment. Women who are diagnosed with ovarian cancer are commonly prescribed two chemotherapy drugs: paclitaxel and carboplatin. When a patient’s body resists these drugs, she is left with few options for continued ovarian cancer treatment. For those who do not experience initial resistance, the looming threat of recurrence suggests future difficulties. Thankfully, the ominous outlook for ovarian cancer treatment is looking brighter thanks to physician-scientist Robert C Bast, Jr, MD., and his past support from the National Foundation for Cancer Research (NFCR).  Acknowledging early funding from the NFCR, Dr. Bast has recently published his research results that provide substantial hope for women undergoing ovarian cancer treatment. In this study Dr. Bast explains that while carboplatin and paclitaxel can be a strong first-line treatment for ovarian cancer, the drugs are curing less than 20% of advanced stage ovarian cancer. However, a small molecule inhibitor can improve the response to paclitaxel in ovarian cancer cells and complex models during the pre-clinical research and the combined treatment is being used now in a Phase I trial for ovarian cancer. In the current paper, the research team discovered that the inhibitor increased carboplatin’s ability to induce DNA-damage and apoptosis (cell suicide), simply meaning the drug’s ability to kill cancerous cells improved. Dr. Bast continues to explain that discovering the impact of the molecular inhibitor on carboplatin provides an exciting outlook for upcoming clinical trials for ovarian cancer treatment. If the ongoing Phase I trial treating ovarian cancer patients with the combination of paclitaxel and the inhibitor goes well, a Phase I/II trial may be initiated using the molecule inhibitor and carboplatin. This exciting discovery suggests that women undergoing ovarian cancer treatment may have a more promising outlook, especially those who experience resistance to carboplatin and paclitaxel or have a recurrence of ovarian cancer. NFCR continues to support world leaders in ovarian cancer research. Amongst these current and past funded scientists are Dr. Danny Welch, Dr. Wei Zhang, Dr. Susan Horwitz, Dr. Amos B. Smith III, and Dr. Harold F. Dvorak. Each dedicated NFCR-funded researcher is committed to game-changing discoveries in cancer treatments, detection, and ultimately, a cure. Visit National Foundation for Cancer Research to learn how you can play a role in supporting world leaders in cancer research. Additional Reads You May Enjoy: Genetic Cues to Ovarian Cancer Explored The Development of Better Ovarian Cancer Biomarkers 5 Warning Signs Women Shouldn’t Ignore Stay connected with us! Receive our monthly e-newsletter and blogs featuring stories of inspiration, support resources, cancer prevention tips and more. Sign up here.