Research by Type:
| Michael Sporn, M.D. |
|
Dartmouth Medical School
Developing New Drugs and Genetic Targets to Stop and Prevent Cancer In order to mount an effective battle against cancer, scientists have first had to develop a clearer understanding a process called carcinogenesis, which is a series of mistakes in cell differentiation that can lead to the formation of malignant tumors. In carcinogenesis, cells undergo step-by-step genetic mutations. During this process, normal cells become slightly abnormal, or premalignant. Allowed to continue along the carcinogenic path, they eventually may become malignant. However, malignant cells do not die as all healthy cells do. Instead, they survive and multiply to form tumors that invade nearby tissue and crowd out normal cells. Malignant cells can also spread to other areas in the body through the blood or lymphatic fluid, starting tumors in new sites.
Project Director Expertise Michael Sporn, M.D., a molecular biologist and pharmacologist at Dartmouth Medical School in Hanover, New Hampshire, has studied ways to prevent cancer since 1957. During his career, he has served as the head of the Lung Cancer Unit and Chief of the Laboratory of Chemoprevention at the National Institutes of Health. Chemoprevention-or the use of medications to stop the development of cancer-has been central to his research. NFCR Research Overview Dr. Sporn's research aims to identify receptors or targets for chemoprevention agents early in the carcinogenic process. By taking this approach, Dr. Sporn can block cancer before it gets started. For example, to fight breast cancer, evidence suggests that tamoxifen interacts with an estrogen hormone receptor to stop cells from becoming malignant. Similarly, other researchers have identified new molecular targets for chemoprevention agents called retinoid receptors, which appear to play a role in carcinogenesis for lung, breast and oral cancers. In addition to discovering new targets for chemoprevention agents, Dr. Sporn is developing new drugs to stop tumor development. Working with a team of researchers, he has developed and refined synthetic retinoids, which attach to retinoid receptors and appear to halt carcinogenesis at several different steps in the process. His studies have shown that retinoids stop the development of secondary tumors in patients who already have had a primary malignancy. In addition, Dr. Sporn has helped to develop estrogen-like substances that also appear to halt carcinogenesis for some tumor types. With support from the National Foundation for Cancer Research, Dr. Sporn has developed several new chemoprevention agents that are directed at specific molecular targets and can help stop cancer as it develops within the cell. His work has shown promising results in test tube and tumor model studies. Working with a team of researchers in the chemistry department at Dartmouth, for example, Dr. Sporn has developed more than 80 different types of triterpenoids, a new class of chemoprevention agents that are related to retinoids and steroids. Two triterpenoids, TP-69 and TP-72, have shown impressive research results in inhibiting the formation of key enzymes that are involved in the carcinogenic process for several kinds of cancer. In other NFCR-sponsored research, Dr. Sporn developed another synthetic triterpenoid, called CDDO. CDDO appears to stop the carcinogenic process during the premalignant and malignant stages in several kinds of cancer by suppressing the formation of inflammatory agents that promote carcinogenesis. Recently, the Sporn team tested CCDO-Me and CCDO-EA in pancreatic cell lines and demonstrated their effectiveness in suppressing inflammatory agents. These triterpenoids also delayed the formation of pancreatic cancer in laboratory models that mimic the disease found in humans. These are some of the very first experiments ever to be published to show effective chemoprevention of pancreatic cancer. For individuals who have a family history of pancreatic cancer or other people at high risk to develop the disease, these promising results offer hope that their chances of developing this devastating cancer may be dramatically reduced by the use of chemoprevention. Treating Cancer with Triterpenoids With NFCR support, Dr. Sporn has conducted an early phase clinical trial for treating patients with lung, pancreatic, and other cancers and leukemia using triterpenoids. The results were highly encouraging and the plan now is to continue clinical testing in the near future. The beauty of Dr. Sporn's basic research was recently demonstrated when patients in the clinical trial had a remarkable improvement in their kidney function from treatment with the triterpenoids. A separate trial is now being conducted that treats Type II diabetes patients who have chronic kidney disease with triterpenoids. This is an inspiring expansion of Dr. Sporn's research that may benefit not only cancer patients, but diabetics as well.
Future Research Goals Dr. Sporn's future research efforts are directed toward finding new and better ways to prevent cancer. He is working to identify the genetic changes that predict increased risk for developing different kinds of cancer.. Finally, he is developing new and innovative treatment plans that use multiple chemoprevention agents to stop the carcinogenic process at several points along the way. Impact on Cancer Prevention, Treatment, or Cure Dr. Sporn has led research efforts that aim to stop cancer before it starts. By identifying molecular targets to stop the carcinogenic process and developing agents to strike those targets, he has made enormous contributions to halting cancer at multiple points during the progression from normal to cancerous cells. His work offers hope that some of the most common and deadly cancers-including breast, lung, and oral cancer-can be defused before they strike and spread tumor cells throughout the body. |
Many researchers--like NFCR Project Director Dr. Michael Sporn--are looking for ways to stop the carcinogenic process. By blocking the genetic damage that initiates carcinogenesis, they hope to prevent cancer before it starts. And even if cells become premalignant, scientists hope to be able to halt cancer formation before it takes hold and starts to spread by reversing the steady march toward malignancy.
