Indiana University School of Medicine researchers make breakthrough discovery in cancer treatment

Researchers at Indiana University’s School of Medicine and their team have shed some light on new insights at the molecular level that could improve treatment options for people with acute myeloid leukemia (or AML). AML is a bone marrow and blood cancer that is both severe and rare. The researchers have found a new chemical compound that was designed to beat gene mutations that have become drug resistant and that also do not have any other current treatments. The team hopes to use this new method to create better outcomes for patients that also last longer against this aggressive form of cancer.

Even as AML is a rare form of cancer, it is still among the most common forms of leukemia found in adults. People diagnosed with acute myeloid leukemia are found to have genetic mutations that create a large amount of abnormal blood cells. The longer this goes untreated, the worse the prognosis becomes, with the five year survival rate for AML among adults sitting around 30%.

The Journal of Clinical Investigation recently published a study in which researchers found blocking agents (also called inhibitors) that target the most common gene mutation in AML, FLT3 gene mutations. 

In an article posted on Indiana University’s Purdue University-Indianapolis website, Baskar Ramdas, PhD, who is a co-author on the study and serves as the IU School of Medicine’s assistant research professor of pediatrics, was quoted about the new discovery, saying, “Despite the widespread occurrence and clinical importance of FLT3 mutations in causing AML, treatment options tailored to this genetic anomaly are scarce. Our goal was to identify new and powerful inhibitors targeting the mutations, particularly those resistant to currently approved FDA options.”

Those FDA approved drugs such as crenolanib and quizartinib are currently being used by patients to attack FLT3 mutations, but over time some of those patients have been found to develop a resistance to those drugs. In a recent study, researchers found two new inhibitors that more successfully target those FLT3 mutations as well as other secondary mutations that were not affected by drug treatments. 

The director of the Indiana University School of Medicine’s Herman B. Wells Center for Pediatric Research, and co-leader of the Hematopoiesis and Hematologic Malignancies program at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Reuben Kapur, PhD, was also a co-author on the study, and was quoted as saying, “Pinpointing where other treatments were causing resistance or relapse led to the development of a new lead compound that will hopefully be a more effective drug in the long run. Our preclinical study results have shown incredible promise, and we’re excited to keep the momentum going so AML patients can have more resilient options.”

Herman Sintim, PhD was also a co-author on the study. He is a Distinguished Professor in Chemistry in the James Tarpo Jr. and Margaret Tarpo Department of Chemistry at Purdue University, as well as  the Richard B. Wetherill Professor of Chemistry and Drug Discovery. He engineered the new compound called HSN748 (patent pending) which will soon see clinical use.

Sintim noted that the data the team was able to gather so far was due to the collaboration between Purdue and Indiana University receiving funding from the National Institutes of Health. The funding will allow for HSN748 to be tested across a number of cancer models and improves the chance for more funding to develop it further. Moving forward, the license holder of HSN748, KinaRX, a new biotechnology company that plans to create more new solutions to drug resistant cancers, is working to get the compound and others on the market. KinaRX is working closely with Kapur who is serving on the scientific advisory board there.

Sintim was also quoted on the partnership between Indiana University, Purdue, and KinaRX, saying, “This academic-industry collaboration between KinaRx, Purdue and IU will continue as we continue determining the mutational backgrounds that are most sensitive to our lead compound HSN748. As the drug progresses to the next phase of clinical trials, the company would like to increase the collaboration with clinicians, including leukemia specialists at IU.”

In addition to the scientists named above, the following people were named as co-authors on the study: M. Javad Aman of KinaRx, Inc, Frederick W. Holtsberg, Chrysi Kanellopoulou; Rena Lapidus and Ashkan Emadi of the University of Maryland; Neetu Dayal, Elizabeth Larocque, Elizabeth Ruth Fei Y. Chu, Rodrigo Mohallem, Saniya Virani, Gaurav Chopra and Uma K. Aryal of Purdue; and Ruchi Pandey, Rahul Kanumuri, Santhosh Kumar Pasupuleti, Sheng Liu, Jun Wan and Laura S. Haneline of IU.

More information about Indiana University School of Medicine can be found at the school’s website.

More information about Indiana University-Purdue University Indianapolis can be found on the school’s website.