Featured Research

from universities, journals, and other organizations

New therapeutic agents that may benefit leukemia patients

Date:
October 4, 2013
Source:
Indiana University
Summary:
An cancer researcher and his colleagues have discovered new therapeutic targets and drugs for certain types of leukemia or blood cancer.

An Indiana University cancer researcher and his colleagues have discovered new therapeutic targets and drugs that may someday benefit people with certain types of leukemia or blood cancer.

Reuben Kapur, Ph.D., the Frieda and Albrecht Kipp Professor of Pediatrics at the IU School of Medicine and a researcher at the Indiana University Melvin and Bren Simon Cancer Center, and colleagues discovered in pre-clinical and pharmacological models that cancer cells with a mutation in the KIT receptor -- an oncogenic/cancerous form of the receptor -- in mast cell leukemia and acute myeloid leukemia can be stopped.

Their findings were published online Sept. 16 in the Journal of Clinical Investigation and appeared in print Oct. 1.

According to Dr. Kapur, activating mutations of KIT receptors are almost always associated with a type of leukemia called mast cell leukemia. The mutations in the KIT receptor are found in about 90 percent of patients with this type of leukemia. In addition, activating mutations of KIT are also exclusively associated with a subtype of acute myeloid leukemia known as core binding factor leukemia. When KIT is associated with these two types of leukemia, the survival rate for patients is profoundly reduced in comparison to patients who do not have this mutation.

Dr. Kapur and colleagues investigated whether they could shut down the growth response that is induced by this mutation.

"We identified two new targets in leukemic cells bearing this mutation, which when targeted or inhibited, cause leukemia cells to die," Dr. Kapur said.

The researchers discovered that the two targets are Rac GTPase and Pak (p21-activated kinase). In return, they designed a novel Rac inhibitor -- EHop-016 -- that is considerably more potent than previously described inhibitors of Rac. They also demonstrated a novel role for Pak inhibition in leukemia using an existing Pak inhibitor.

Both are being tested in pre-clinical models to further examine their growth inhibitory properties as well as long-term treatment-associated toxicity.

Dr. Kapur said treatments for leukemia have remained mostly unchanged in the past 30 years. Thus, researchers continue to search for better and more effective ways to treat this debilitating disease.

"We've been looking for new targets and new ways of treating leukemia and special types of leukemias," Dr. Kapur said. "Leukemia is an extremely complex disease. It's a combination of multiple alterations in the patient's DNA, which eventually results in leukemia. Therefore, it will be very difficult to cure leukemia with just one drug. It will have to be a combination of multiple drugs, if we're to cure this disease."

Dr. Kapur is also professor of biochemistry and molecular biology, of medical and molecular genetics, and of microbiology and immunology at the IU School of Medicine.

Principal authors of the study were Suranganie Dharmawardhane and Cornelis P. Vlaar of the Department of Pharmaceutical Sciences at the University of Puerto Rico; Ramon V. Tiu and Valeria Visconte of the Taussig Cancer Institute, Cleveland Clinic; Ray R. Mattingly of Wayne State University; Joydeep Gosh, Emily Sims, Baskar Ramdas, Anindya Chatterjee, Raghuveer Singh Mali and Holly Martin of the IU Department of Pediatrics, Herman B Wells Center for Pediatric Research; and Veerendra Munugalavadla of the Department of Cancer Immunotherapy and Hematology, Genentech Inc.

This study was supported, in part, by grants from the National Institutes of Health (R01HL077177, R01HL075816 and R01CA134777 to R. Kapur), F31AG040974 (to H. Martin) and T32HL007910 (to A. Chatterjee); a grant from the American Cancer Society (PF13-065-01 to A. Chatterjee); and a grant from Riley Children's Foundation (to R. Kapur).


Story Source:

The above story is based on materials provided by Indiana University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Holly Martin, Raghuveer Singh Mali, Peilin Ma, Anindya Chatterjee, Baskar Ramdas, Emily Sims, Veerendra Munugalavadla, Joydeep Ghosh, Ray R. Mattingly, Valeria Visconte, Ramon V. Tiu, Cornelis P. Vlaar, Suranganie Dharmawardhane, Reuben Kapur. Pak and Rac GTPases promote oncogenic KIT–induced neoplasms. Journal of Clinical Investigation, 2013; 123 (10): 4449 DOI: 10.1172/JCI67509

Cite This Page:

Indiana University. "New therapeutic agents that may benefit leukemia patients." ScienceDaily. ScienceDaily, 4 October 2013. <www.sciencedaily.com/releases/2013/10/131004154345.htm>.
Indiana University. (2013, October 4). New therapeutic agents that may benefit leukemia patients. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2013/10/131004154345.htm
Indiana University. "New therapeutic agents that may benefit leukemia patients." ScienceDaily. www.sciencedaily.com/releases/2013/10/131004154345.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins