Navigation Links
Smac-ing lung cancer to death
Date:11/12/2007

Howard Hughes Medical Institute researchers have developed a small molecule that can turn the survival signal for a variety of cancer cells into a death signal. The molecule mimics the activity of Smac, a protein that triggers the suicide of some types of cancer cells.

The researchers say their findings suggest that Smac-mimetic compounds could be useful as targeted cancer treatments for lung and other cancers. Such therapy may be less toxic to healthy cells than current compounds used in cancer chemotherapy.

The researchers, led by Howard Hughes Medical Institute investigator Xiaodong Wang, published their findings in the November, 2007, issue of the journal Cancer Cell. Wang is at the University of Texas Southwestern Medical Center.

Cells that are defective or that become unnecessary during growth and development are induced to commit suicide through a finely balanced process known as apoptosis, or programmed cell death. A protein called Smac, which is a shortened version of second mitochondria-derived activator of apoptosis, is a part of the cells programmed cell death machinery. When that machinery is switched on, Smac is released from the mitochondria and triggers the pathway that kills damaged or abnormal cells. Cancer cells, however, can survive Smacs death signal by switching off the apoptotic machinery.

To see if they could get around this problem, Wang and other researchers have developed small-molecule mimetics of Smac that can enter the cell and trigger apoptosis. These mimetic molecules do their damage without the need for the Smac signal from the mitochondria. In earlier studies, Wang and his colleagues found that a Smac mimetic that they developed in the lab could kill cancer cells in culture. But they found that the cancer cells are only killed when the mimetic molecule is introduced in conjunction with another component of the apoptotic machinery known as TNF.

In the new studies published in Cancer Cell, Wang and his colleagues found that a significant percentage of human non-small-cell lung cancer cell lines were sensitive to treatment by the Smac mimetic alone. When the researchers introduced those sensitive cells into mice and allowed them to produce tumors, they found that the Smac mimetic caused the tumors to regress and, in some cases, even disappear.

These findings made us wonder what it was about these cell lines that made them sensitive to the Smac mimetic alone, said Wang. Cancer cells are hard to kill, but these cell lines seemed to have already become sensitized to apoptosis.

The researchers studies revealed that the sensitive cell lines produced their own TNF, so they were already primed for apoptosis. The paradox, said Wang, is that TNF signaling is also part of a complex pathway that gives cancer cells a survival signal, offering them a growth advantage. The researchers also found that some breast cancer and melanoma cell lines were sensitive to the Smac mimetic alone.

Thus, in these cancer cell lines, the TNF survival advantage turns out to be a fatal flaw, because the same pathway can be switched to apoptosis by Smac mimetics, said Wang. So, for some cancers, we might be able to use Smac mimetics as a single treatment agent. And we can use the presence of TNF as a marker to tell us which tumors will respond to the Smac mimetic alone.

People have been suspecting for a long time that some cancer cells may somehow turn on their apoptotic pathway already, said Wang. And now we know what pathway they turn on and why. We can take advantage of this phenomenon for potential cancer therapy by switching a signal into a deadly one with Smac mimetics.


'/>"/>

Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
Source:Eurekalert

Related medicine news :

1. Conventional prognostic factors fail to explain better prostate cancer survival in most Asian men
2. Survival differences by race most apparent in advanced stages of breast cancer
3. MRI finds breast cancer before it becomes dangerous
4. Investigators uncover intriguing clues to why persistent acid reflux sometimes turns into cancer
5. Pathway links inflammation, angiogenesis and breast cancer
6. Radiologists encouraged to look beyond cancer for clinically unseen diseases
7. Diet high in meat, fat and refined grains linked to risk for colon cancer recurrence, death
8. Immune deficiency linked to a type of eye cancer
9. Drop in breast cancer incidence linked to hormone use, not mammograms
10. Breast cancer prevention practices vary across Canada
11. First biomarker discovered that predicts prostate cancer outcome
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... ... Austin residents seeking Mohs surgery services, can now turn to Dr. Jessica ... Peckham for medical and surgical dermatology. , Dr. Dorsey brings specialization to include Mohs ... Mohs Micrographic Surgery completed by Dr. Dorsey was under the direction of Glenn Goldstein, ...
(Date:6/25/2016)... Oklahoma (PRWEB) , ... June 25, 2016 , ... ... both athletes and non-athletes recover from injury. Recently, he has implemented orthobiologic procedures ... Oklahoma City area —Johnson is one of the first doctors to perform the ...
(Date:6/24/2016)... ... June 24, 2016 , ... June 19, 2016 is World Sickle ... chronic pain and the benefits of holistic treatments, Serenity Recovery Center of ... Sickle Cell Disease. , Sickle Cell Disease (SCD) is a disorder of the red ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San Diego, CA ... the Road To Recovery® program to drive cancer patients to and from their cancer ... ensure the highest quality of life and ongoing independence. Getting to and from ...
(Date:6/24/2016)... ... June 24, 2016 , ... Puradigm® ... Group (TGIG), has initiated cultivation and processing operations at its production facility, and ... Nevada. , Puradigm is the manufacturer of a complete system of proactive air ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ ) ... Improvements Act of 1976, as amended ("HSR"), with respect ... Nasdaq: CPXX ) expired effective June 24, ... As previously announced on May 31, 2016, Jazz Pharmaceuticals ... which Jazz Pharmaceuticals has commenced a tender offer for ...
(Date:6/24/2016)... SAN FRANCISCO, Calif. , June 24, 2016 ... GBT ), a biopharmaceutical company developing novel therapeutics ... significant unmet needs, today announced the closing of ... shares of common stock, at the public offering ... shares in the offering were offered by GBT. ...
(Date:6/24/2016)... June 24, 2016 Dehaier Medical Systems Ltd. ... which develops, markets and sells medical devices and wearable ... signed a strategic cooperation agreement with Hongyuan Supply Chain ... Chain") on June 20, 2016, to develop Dehaier,s new ... cooperation agreement, Dehaier will leverage Hongyuan Supply Chain,s sales ...
Breaking Medicine Technology: