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New Way to Stop Cancer? Block Their Recycling System, and Tumor Cells Die.

Summary: TEHRAN (FNA)- 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 autophagy /au·toph·a·gy/ (aw-tof´ah-je)
1. lysosomal digestion of a cell's own cytoplasmic material.

2. autophagia.


autophagy

1. lysosomal digestion of a cell's own cytoplasmic material.

2.
, 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 (body, education) University of Pennsylvania - The home of ENIAC and Machiavelli.

http://upenn.edu/.

Address: Philadelphia, PA, USA.
, 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 chloroquine /chlo·ro·quine/ (klor´o-kwin) an antiamebic and anti-inflammatory used in the treatment of malaria, giardiasis, extraintestinal amebiasis, lupus erythematosus, and rheumatoid arthritis; used also as the hydrochloride and . 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, ATG ATG antithymocyte globulin.
lymphocyte immune globulin (antithymocyte globulin equine, ATG, ATG equine, LIG)

Atgam

Pharmacologic class: Immunoglobulin

Therapeutic class: Immunosuppressant
16L1, 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 Adv. 1. in the meantime - during the intervening time; "meanwhile I will not think about the problem"; "meantime he was attentive to his other interests"; "in the meantime the police were notified"
meantime, meanwhile
, though, Amaravadi says the work illustrates just how important autophagy is to cancer cells, and provides an important new step for future therapies.

2012 Fars News Agency Fars News Agency (FNA) is an Iranian news agency. It was officially launched in Tehran in February 2002 to "promote the principles of the Islamic Revolution and safeguard national interests". . All rights reserved

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Publication:FARS News Agency
Date:May 9, 2012
Words:463
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