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:2/18/2017)... ... February 17, 2017 , ... Focused ... innovation in the industry, according to the recent NEJM Catalyst Insights Report on ... of the NEJM Catalyst Insights Council, a qualified group of U.S. executives, clinical ...
(Date:2/18/2017)... ... 2017 , ... A new directory from the Senior Veterans ... connect elderly veterans of America's armed forces to a range of senior care ... on this year's increase in the Veterans Pension with Aid & Attendance for ...
(Date:2/17/2017)... ... 2017 , ... For the first time, International Scholarship and ... floor for the 2017 HIMSS Conference & Exhibition at the Orange ... than 40,000 healthcare industry professionals are expected at the conference, where they will ...
(Date:2/17/2017)... ... February 17, 2017 , ... Access today ... Exhibition in Orlando, Fla., February 19-23. Visitors to the company’s booth (#1778) will ... used electronic patient signatures solution in healthcare . , Since it first ...
(Date:2/17/2017)... ... February 17, 2017 , ... Cancer diagnostics workflow solution provider ... 20 – 22 in San Francisco. As part of the Tri-Conference expo, which ... workflow solution, as well as its new precision medicine platform, “Crosswalk Insight: Oncology™.” ...
Breaking Medicine News(10 mins):
(Date:2/16/2017)... 2017  AcelRx Pharmaceuticals, Inc. (Nasdaq: ... the development and commercialization of innovative therapies for ... Vincent J. Angotti has been appointed ... company,s board of directors, effective Monday, March 6, ... experience leading executive and commercial teams at public ...
(Date:2/16/2017)... , Feb. 16, 2017  Prescription pain medications ... department visit are necessary for long-term opioid use to ... Feb. 16 th edition of The New ... "Emergency physicians see more patients in acute pain than ... Parker , MD, FACEP, president of the American College ...
(Date:2/16/2017)... Research and Markets has announced the addition of the ... Function, Application, Cancer Type, Technology - Forecast to 2025" report ... ... grow at a CAGR of around 28.6% over the next decade ... Some of the prominent trends that the market is witnessing include ...
Breaking Medicine Technology: