Navigation Links
How 'IAP antagonist' chemicals kill tumors
Date:11/15/2007

Chemical compounds specially designed to neutralize proteins that would otherwise allow tumor cells to cheat death have been recognized for some time by scientists as a promising new avenue for cancer therapy. Now, two studies in the November 16, 2007 issue of the journal Cell, a publication of Cell Press, provide insight into just how these antagonists of the anti-deathso-called Inhibitor-of-Apoptosis (IAP)proteins work to fight tumors.

The researchers reveal that the compounds hit specific IAP proteins known as cIAPs. That came as a surprise, they said, because the chemicals had originally been designed to target another of the anti-death proteins. The studies further show that the small molecule inhibitors not only block the death-defying proteins, but they also actively engage other players that lead to the death of tumor cells. Meanwhile, the chemicals seem to have little effect on healthy cells.

There has been an effort for several years to look for IAP antagonists, which seem to be very good in causing cell death in cancer, said Domagoj Vucic of Genentech, Inc. in South San Francisco, who led one of the two studies. It was thought they might be used in combination with other drugs. But now, we show that these chemicals are capable of inducing apoptosis all on their own.

It appears that when you remove cIAP1 in sensitive cancer cells, it opens the tap and everything just goes [toward cell death], added John Silke of La Trobe University in Australia, who led the other study. cIAP1 seems to be critical in deciding the life-or-death balance.

Apoptosis or programmed cell death is a cell suicide mechanism with a major role in development and homeostasis in all animals, Vucic explained. It is now accepted that apoptosis is also an extremely important defense against tumors, Silke added.

Scientists initially discovered the IAP proteins capable of blocking cell death in, of all things, a caterpillar virus, Silke said. The IAP proteins were later found in other organisms, from flies to mammals. The proteins were also shown to rise in human cancer, making them attractive targets for the development of novel cancer therapeutics. Scientists have therefore sought to design molecules that could antagonize IAPs, taking the lead from natural IAP antagonists.

Vucics group now shows that an IAP antagonist leads cIAPs to be marked for degradation by cellular components known as proteosomes. This is an amazingly rapid occurrence, happening within two minutes in cells in culture after exposure to the compound, said Vishva Dixit, who is also from Genentech.

They found that treatment with the IAP antagonist led to the activation of a NF-"B pathway that produces another protein, called tumor necrosis factor (TNFa). TNFa comes back and binds its receptor, triggering unimpeded apoptosis and killing cancer cells, Vucic said.

Likewise, Silkes team showed that synthetic and naturally occurring IAP antagonists kill susceptible tumor cells through their action on cIAP1, resulting in NF-"B activation, which drives TNFa production and initiates tumor cell death. Silke noted that the congruence between the findings of the two studies is a really good sign.

These studies show the potential for these drugs, although there is a long road to go, Silke added. It also demonstrates an important principle: If you can understand how something works through basic scientific discoveries, then you can really start to make targeted tumor therapies. We can begin to understand how tumors live and how to make them die.

Vucic said that a phase I clinical trial designed to test the safety of one of their IAP antagonist compounds in human patients is already underway.


'/>"/>

Contact: Cathleen Genova
cgenova@cell.com
617-397-2802
Cell Press
Source:Eurekalert

Related medicine news :

1. Rohm and Haas to Webcast Presentation at Credit Suisse Chemicals Conference
2. National Academies advisory: genes and toxic chemicals
3. Genomic technologies to identify toxic chemicals should be developed
4. Researchers study potential health benefits of natural chemicals in muscadine grape seeds
5. Study reveals huffing household chemicals connected to teen suicide
6. Marijuana-like brain chemicals work as antidepressant
7. Hazardous Advanced Micro Devices (A.M.D.) Clean Room Chemicals Caused Multiple Birth Defects, Lawsuit Alleges
8. Tumors use enzyme to recruit regulatory T-cells and suppress immune response
9. Study suggests brain tumors need treatment with multiple targeted drugs
10. Bright tumors, dim prospects
11. Genomic profiling of lung tumors helps doctors choose most effective treatment
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/24/2017)... CA (PRWEB) , ... February 24, 2017 , ... ... for qualifying into the Senior International Elite division on February 12th. Ms. ... Around divisions at the elite qualifier competition held in Las Vegas, Nevada. Frida ...
(Date:2/23/2017)... (PRWEB) , ... February 23, 2017 , ... ... Department of Justice jointly issued a letter to withdraw previous guidance ... with their gender identity. The guidance issued in May 2016 by the Obama ...
(Date:2/23/2017)... ... February 23, 2017 , ... Rare Disease Report®, ... be participating in Rare Disease Day events, hosted by the Rare Disease Legislative ... Report, a website, weekly e-newsletter and quarterly publication, will be conducting interviews with ...
(Date:2/23/2017)... (PRWEB) , ... February 23, 2017 , ... Hamlin Dental ... announce that they are sponsoring a raffle. Throughout the month of February, patients who ... receive a gift card for a dinner for two at the Cheesecake Factory. ...
(Date:2/23/2017)... ... February 23, 2017 , ... On April 13, 2017, ... “Doping in Sport: How the Culture Might Change,” in conjunction with ... symposium will be held at Pepperdine University in Malibu, California. , Sir Philip ...
Breaking Medicine News(10 mins):
(Date:2/24/2017)... Following receiving CE Marking in Europe ... AMAR is a major milestone for the country where the device was developed ... market in Israel   ... inclusion in the National Health Basket , Israel , ... E-QURE Corp. (OTCQB: EQUR), a leader in medical devices for the treatment of advanced wound ...
(Date:2/24/2017)... Research and Markets has announced the addition of the ... report to their offering. ... The Global Empty Capsules Market is poised to grow at a ... billion by 2025. This industry report analyzes the market ... as regional levels presented in the research scope. The study provides historical ...
(Date:2/24/2017)... , Feb. 24, 2017 Physician General ... Drug and Alcohol Programs Jennifer Smith commended ... providing training for and using naloxone, a life-saving overdose ... McCullough , a recovery specialist and overdose survivor who ... EMS providers. "A significant part of fighting ...
Breaking Medicine Technology: