Navigation Links
Block its recycling system, and cancer kicks the can, according to new Penn study
Date:5/8/2012

PHILADELPHIA - All cells have the ability to recycle unwanted or damaged proteins and reuse the building blocks as food. But cancer cells have ramped up the system, called autophagy, and rely on it to escape damage in the face of chemotherapy and other treatments. Now, researchers at the Perelman School of Medicine; the Abramson Cancer Center; and the School of Arts and Sciences, at the University of Pennsylvania, have developed a potent new drug that clogs up the recycling machinery and kills tumor cells in mouse models.

Ravi K. Amaravadi, MD, assistant professor of Medicine, and colleagues showed previously that an old malaria drug, hydroxychloroquine, reduces autophagy in cancer cells and makes them more likely to die when exposed to chemotherapy. The strategy is currently being tested in clinical trials, and preliminary results are promising. The catch, though, is that it's not always possible to give patients a high enough dose of hydroxychloroquine to have an effect on their tumor cells.

Amaravadi teamed up with Jeffrey Winkler, PhD, the Merriam Professor of Chemistry, to design a series of more potent versions of chloroquine. They describe the design, chemical synthesis, and biological evaluation of a highly effective, new compound called Lys05, in the early edition of the Proceedings of the National Academy of Sciences this week.

Unlike hydroxychloroquine, which has little impact on tumor cells when used as a single agent, the new drug, called Lys05, slows tumor growth in animal models even in the absence of other anti-tumor therapies. What's more, the Lys05 dose that is toxic to cancer cells, which are addicted to recycling and rely on it much more heavily than healthy cells, has little or no effect on healthy cells.

"We see that Lys05 has anti-tumor activity at doses that are non-toxic for the animals," Amaravadi says. "This single-agent anti-tumor activity suggests this drug, or its derivative, may be even more effective in patients than hydroxychloroquine." Remarkably, however, when the investigators increase the dose of Lys05, some animals develop symptoms that mimic a known genetic deficiency in an autophagy gene, ATG16L1, which affects some patients with Crohn's disease . That similarity technically called a phenocopy clearly shows that Lys05 works by interfering with the recycling system in cells.

Lys05, and its companion compound Lys01, aren't quite ready for testing in patients, according to Amaravadi. Before that can happen, the molecules need to be optimized and undergo more toxicity testing in animals. Amaravadi and Winkler hope to team up with an industry partner for that portion of the project.

In the meantime, though, Amaravadi says the work illustrates just how important autophagy is to cancer cells, and provides an important new step for future therapies.


'/>"/>
Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

Related medicine news :

1. Penn study cautions use of drugs to block niacin flush
2. Red wine, fruit compound could help block fat cell formation
3. Novel drug in pill form safer than standard approach to treat blocked lung blood vessels
4. Judge Blocks Plan for Graphic Cigarette Warnings
5. Blocking telomerase kills cancer cells but provokes resistance, progression
6. Stents and surgery for blocked neck arteries are neck-and-neck as lasting stroke prevention
7. Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells
8. Drug-Coated Balloons Open Arteries Blocked by Narrowed Stents
9. Lipid blocks influenza infection
10. Judge Blocks FDA Plan for Graphic Cigarette Warnings
11. Inadequate supply of protein building blocks may explain pregnancy failures in bovine cloning experiments
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2017)... ... June 27, 2017 , ... Children’s National Health System received top honors in ... program ranking #1 out of more than 1500 neonatal intensive care units coast ... Roll, a distinction given to the top performing children’s hospitals in the country. ...
(Date:6/26/2017)... (PRWEB) , ... June 26, 2017 , ... ... according to a recent review of government data released by the United Soybean ... in management practices, Maryland’s soybean farmers have increased their productivity on less land ...
(Date:6/26/2017)... WI (PRWEB) , ... June 26, 2017 , ... New ... consultations from Dr. Angela Cotey, with or without a referral. Dr. Cotey is a ... benefits of this preferred tooth replacement option. , Patients with missing teeth in Fitchburg, ...
(Date:6/25/2017)... New Orleans (PRWEB) , ... June 25, 2017 , ... ... ARM Meeting in New Orleans. This is a new, greatly improved version of ... of Information Act (FOIA) requests by Fred Trotter and subsequently called the the “Doctor ...
(Date:6/24/2017)... (PRWEB) , ... June 24, 2017 , ... ... Dental365 family. Located at 217 Portion Road in Lake Ronkonkoma, Dental365 offers patients ... and weekends so that visits to the dentist fit into their patients’ busy ...
Breaking Medicine News(10 mins):
(Date:6/20/2017)... HILLS, Calif. , June 20, 2017 SkylineDx ... the use of MMprofiler with SKY92, the company,s prognostic ... In a poster presentation at the 22 nd ... Madrid, Spain , SkylineDx researchers will demonstrate ... patients. In a separate e-poster presentation ...
(Date:6/19/2017)... 2017  Researchers from DRUGSCAN ® and INC ... a live, complimentary webinar titled, "Untangling methods to tamper ... real world" on Wednesday June 28, 2017 from 12:00 ... webinar will feature interviews with recreational and dependent prescription ... techniques abusers use to prepare opioid tablets for routes ...
(Date:6/16/2017)... , June 16, 2017  Exactly 50 years ago today, ... what later became known as the San Francisco "Summer of ... is unveiling two radical innovations in strategic market research portals ... announcement marks the beginning of Northern Light,s "Summer of Love ... ...
Breaking Medicine Technology: