One of the things that makes cancer so formidable – and so difficult to treat – is the fact that cancer cells literally refuse to die. In a healthy organism, abnormal cells are removed through a process of programmed cell death known as apoptosis. But in cancer cells, the apoptosis pathways are defective, allowing cancer cells to thrive and, often, making them resistant to conventional therapy.
Targeting those defective pathways – and reinstating the process of apoptosis in cancer cells – has long been the research objective of Dr. Shaomeng Wang, U-M professor of medicine, pharmacology and medicinal chemistry.
Recently Wang published a new study showing significant progress toward creating small molecule therapeutics that attack cancer cells by restarting the normal process of apoptosis, with few side effects.
In the study, Wang led a team of researchers at the University of Michigan Comprehensive Cancer Center in development of a new drug called AT-406 with potential to treat multiple types of cancer. The study, published in the Journal of Medicinal Chemistry, showed that AT-406 effectively targets proteins that block apoptosis, and restores normal cell death. The researchers believe the drug could potentially be used alone or in combination with other treatments. In animal models the drug shrank tumors but caused few side effects. The drug is designed to be taken by mouth which researchers say will make it easier to administer than traditional intravenous chemotherapies.
A second recent study reported early success for new drug compounds developed by Wang and his colleagues at U-M that shrank tumors in mouse models of human cancer. The study looked at two compounds designed to activate a protein, p53, that is kills cancer cells, but is often inactivated in human cancers.
For a fuller description, see http://www.uofmhealth.org/News/cancer_mdm2_0406
“It has always been my goal and desire to translate discoveries from the laboratory to the clinic,” Wang says.
In 2003, Wang joined forces with Drs. Marc E. Lippman and Dajung Yang, both U-M professors at the time, to found Ascenta Therapeutics which to date has attracted $100 million in three rounds of funding. Ascenta has advanced two anticancer drugs into Phase I and II clinical development. Ascenta also has signed a global development and research agreement with sanofi-aventis to develop MDM2 inhibitors discovered by U-M researchers, which could yield as much as $398 million in milestone payments for Ascenta, plus additional royalties on sales.
Wang also launched a second-start up, Ascentage Pharma Group, to develop new anticancer drugs discovered in his U-M lab.
U-M Tech Transfer worked with Wang to facilitate the process of creating the start-ups. “Tech Transfer was extremely helpful in developing flexible mechanisms that allowed the company both to license multiple technologies and to provide ongoing research support.”