Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tumor mutations can predict chemo success

10.08.2009
Genetic profiling of tumors could have 'immediate impact' on treating cancer

New work by MIT cancer biologists shows that the interplay between two key genes that are often defective in tumors determines how cancer cells respond to chemotherapy.

The findings should have an immediate impact on cancer treatment, say Michael Hemann and Michael Yaffe, the two MIT biology professors who led the study. The work could help doctors predict what types of chemotherapy will be effective in a particular tumor, which would help tailor treatments to each patient.

"This isn't something that's going to take five years to do," says Yaffe, who, along with Hemann is a member of the David H. Koch Institute for Integrative Cancer Research at MIT. "You could begin doing this tomorrow."

The work could also guide the development of new chemotherapy drugs targeted to tumors with specific genetic mutations.

Hemann, Yaffe, and their colleagues report their results in the Aug. 15 issue of the journal Genes and Development. Koch Institute postdoctoral associates Hai Jiang and H. Christian Reinhardt are lead authors of the study, which the researchers say is one of the first examples of how genetic profiling of tumors can translate to improvements in patient treatment.

"There's a huge amount of genetic information available, but it hasn't made its way into clinical practice yet," says Hemann.

Genetic mystery

The research team focused on two proteins often involved in cancer, p53 and ATM. One of the first tumor suppressor genes discovered, p53 serves a watchdog function over a cell's genome, activating repair systems when DNA is damaged and initiating cell death if the damage is irreparable.

ATM is also involved in controlling the cell's response to DNA damage and is known to help regulate p53.

Mutations in p53, ATM or both are often seen in tumor cells. (ATM mutations occur in about 15 percent of cancers, and p53 is mutated in about 30 percent.)

Scientists have long tried to pin down a relationship between mutations in these genes and the effectiveness of DNA-damaging chemotherapy agents, but published studies have produced conflicting reports.

"It's been unclear whether the loss of p53 made tumors easier to treat or harder to treat. You could find examples of either case in the clinical literature," says Yaffe, adding that the same holds true for ATM.

The new study, conducted with human cancer cells, shows that tumors in which both p53 and ATM are defective are highly susceptible to chemotherapy agents that damage DNA. The double mutation prevents tumor cells from being able to repair DNA, and the cells commit suicide.

However, in cells where p53 is mutated but ATM is not, that type of chemotherapy is less effective. Remarkably, tumors where ATM is mutated but p53 is not turn out to be highly resistant to those types of chemotherapy.

With this new information, doctors could choose chemotherapy treatments based on the status of the p53 and ATM genes in a patient's tumor. Traditional DNA-damaging chemotherapy would be a good option for patients with both p53 and ATM mutations, but not for those with normal p53 and mutated ATM.

For patients who have normal ATM and mutated p53, other options might be better: New drugs that inhibit ATM, now in clinical trials, could improve tumors' susceptibility to chemotherapy in those patients.

The study shows the importance of studying cancer genes as a network, rather than trying to predict outcomes based on the status of single genes such as p53, says Robert Abraham, director of the cancer drug discovery program at Wyeth Pharmaceuticals.

Once ATM inhibitors are approved, "understanding the combined status of ATM and p53 should allow physicians to identify patients who should be treated with ATM inhibitors and chemotherapy and those for whom such a therapy could potentially be harmful," Abraham says.

In patients with normal p53 and mutated ATM, doctors could use drugs that target alternative DNA repair pathways. In their Genes and Development paper, the MIT researchers showed that treating such tumors with a drug that targets DNA-PK, another protein involved in DNA repair, renders them vulnerable to chemotherapy.

The MIT researchers collaborated with scientists from the Centre for Genotoxic Stress Research in Denmark, Helsinki University Central Hospital in Finland, and Uppsala University Hospital in Sweden.

The research was funded by the National Institutes of Health, the David H. Koch Fund, the Deutsche Forschungsgemeinschaft, the Deutsche Nierenstiftung, the Danish Cancer Society, the European Community, the Czech Ministry of Education and the Helsinki University Central Hospital Research Fund.

Jen Hirsch | EurekAlert!
Further information:
http://www.mit.edu

More articles from Life Sciences:

nachricht At last, butterflies get a bigger, better evolutionary tree
16.02.2018 | Florida Museum of Natural History

nachricht New treatment strategies for chronic kidney disease from the animal kingdom
16.02.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>