Navigation Links
Cancer cells need normal, nonmutated genes to survive

BOSTON, Mass. (May 28, 2009) Corrupt lifestyles and vices go hand in hand; each feeds the other. But even the worst miscreant needs customary societal amenities to get by. It's the same with cancer cells. While they rely on vices in the form of genetic mutations to wreak havoc, they must sustain their activity, and that requires equal parts vice and virtue.

According to a new study in the May 29 issue of Cell, cancer cells rely heavily on many normal proteins to deal with stress and maintain their deviant state. Researchers at Harvard Medical School and Brigham and Women's Hospital used a technique called RNA interference (RNAi) to dial down the production of thousands of proteins and determine which were required for cancer cell survival.

"Cancer cells actually leverage many genes that don't harbor mutations to maintain their malignant lifestyles," says first author and postdoctoral researcher Ji Luo. "These genes probably help them deal with the problems that develop as a result of the inappropriate presence of growth and survival signaling in tumor cells."

Being a cancer cell isn't easy. Think of all the DNA replication and protein production involved, not to mention the abnormal architecture of a tumor, which deprives cells of oxygen. Survival requires a complete kit of stress response tools.

"Researchers often characterize cancer cells as oncogene addicts, but they're just as reliant on normal genes that alleviate stress," explains senior author Stephen Elledge, a professor at HMS and Brigham and Women's Hospital. "These stress management genes deserve attention as potential therapeutic targets."

In recent years, the National Cancer Institute has supported an ambitious effort to understand the molecular basis of cancer by sequencing cancer genomes. Elledge and Luo note that this Cancer Genome Atlas project would miss the stress management genes.

"If these genes are intact, they won't stand out when you compare the DNA sequences of cancer cells with normal cells," says Luo.

So the team took a different approach to test their "non-oncogene addiction" hypothesis. They acquired two human cell lines, identical in every way except for onethe presence or absence of a Ras oncogene. Ras mutations are prevalent in many deadly cancers, and researchers have not been successful in developing drugs against the dangerous gene.

The team used molecules called shRNAs to interfere with the production of thousands of normal, healthy proteins in the two cell lines. They gave the cells time to divide and sifted through the data to determine which proteins were required for survival. (In the past, labs relied on large robots to complete these types of screens, but Elledge and others have refined the technology in an effort to make RNAi affordable and accessible. Luo conducted his genome-wide screen in test tubes without the aid of a robot.)

Despite their similarities, the two cell lines responded differently to a number of shRNAs. That is, normal cells tolerated low levels of a particular protein while cells with the Ras mutation perished. Luo validated 50 of these hits in a second pair of cell lines. Dozens of these represent brand new therapeutic targets.

"This opens the door to using a drug cocktail approach to treat tumors driven by Ras mutations," says Elledge, who is also an investigator with Howard Hughes Medical Institute. "We might be able to tinker with the levels of these proteins and cripple cancer cells without hurting normal cells in the body, though this needs to be tested in tumor models."

"This type of functional approach complements the physical mapping of cancer genomes, but provides a much more direct path to new anti-cancer drug targets," adds Luo. "The genes that are critical for maintaining the malignant state will really crystallize when we combine forces."


Contact: Alyssa Kneller
Harvard Medical School

Related medicine news :

1. The vulnerable cancer cell
2. New survey highlights growing concern about risk of infection in cancer patients
3. Cancer Survivors Can Still Be Fit, Study Asserts
4. New blood test greatly reduces false-positives in prostate cancer screening
5. Cardiovascular fitness not affected by cancer treatment
6. Cottonseed-based drug shows promise in treating severe brain cancer
7. Peregrine Pharmaceuticals Reports Progress in Cotara(R) Brain Cancer Clinical Program
8. Poniard Pharmaceuticals Announces Positive Efficacy and Safety Data From Phase 2 Clinical Trial of Picoplatin in Men With Metastatic Prostate Cancer
9. Phase 3 Trial Initiated to Evaluate Combination Therapy of Nexavar(R) and Tarceva(R) in Patients with Liver Cancer
10. LIVESTRONG and Penn Medicine announce partnership to bring online care plan tool to cancer survivors
11. Heat Therapy May Help Prevent Esophageal Cancer
Post Your Comments:
(Date:10/13/2017)... ... October 13, 2017 , ... ... process to promote standards of excellence for the field of eating disorders, announces ... 22 – 25, 2018 in Orlando, Florida at the Omni Resort at ChampionsGate. ...
(Date:10/13/2017)... ... October 13, 2017 , ... Many families have long-term insurance that ... insurance companies have a waiver for care if the client has a cognitive impairment ... family pays for care, is often waived, so the benefits from their insurance start ...
(Date:10/13/2017)... ... 13, 2017 , ... Talented host, actor Rob Lowe, is ... a new episode of "Success Files," which is an award-winning educational program broadcasted ... each subject in-depth with passion and integrity. , Sciatica occurs when the sciatic ...
(Date:10/12/2017)... San Francisco, CA (PRWEB) , ... October 12, ... ... and Dr. Cheng, are now treating sleep apnea using cutting-edge Oventus ... sleep apnea, a serious sleep disorder characterized by frequent cessation in breathing. Oral ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... ... AccentCare, a leader in post-acute health care, have expanded their existing home health ... Home Health. , AccentCare has been operating a joint venture home health company ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... WASHINGTON , Sept. 28, 2017 Cohen ... to advance the use of wearable and home sensors ... brain disorders. Early Signal Foundation, a nonprofit organization focused ... populations, will provide an affordable analytical system to record ... ...
(Date:9/25/2017)... R.I. , Sept. 25, 2017  EpiVax, ... assessment, vaccine design, and immune-engineering today announced the ... on the development of personalized therapeutic cancer vaccines. ... has provided exclusive access to enabling technologies to ... Eng., MBA will lead EpiVax Oncology as Chief ...
(Date:9/19/2017)... 19, 2017 HistoSonics, Inc., a venture-backed medical device company developing a non-invasive, robotically ... announced three leadership team developments today:   ... ... Tom ... Veteran medical device executive Josh Stopek , PhD, who ...
Breaking Medicine Technology: