Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Residual tumor cells are a barrier to targeted cancer therapeutics

05.01.2005


Over the past five years, so-called molecularly targeted therapies for cancer have held out great promise. These therapies are based on blocking a cancer-causing genetic pathway that has been turned on in a tumor, thereby allowing it to proliferate and grow in an uncontrolled manner. For a small number of cancers, chronic treatment with molecularly targeted therapies has been shown to be effective in the clinic – at least in the short-term. Recently, based on animal models, several investigators have proposed that chronic treatment – possibly even brief treatment – with molecularly targeted therapies might eliminate cancers. Curing cancers with short-term treatment, however, contrasts sharply with clinical experience with cancer patients, say Penn researchers. This suggests that tumors often become resistant to therapy by finding a way around the genetic blockade.



Using a model for breast cancer, researchers in the Abramson Family Cancer Research Institute of the University of Pennsylvania report that after blocking the gene c-MYC, which is commonly overexpressed in human breast cancers, the tumor still persists. Senior author Lewis A. Chodosh, MD, PhD, Associate Professor, Departments of Cancer Biology and Medicine, and colleagues report their findings in the December issue of Cancer Cell.

Specifically, the group found that after turning off c-MYC in a mouse model, 50 percent of c-MYC-induced mammary cancers were still able to grow. They also found that residual cancer cells persisted in all animals – even those that were seemingly cancer-free. These residual cells quickly recovered their malignant properties either spontaneously or after the researchers reactivated MYC. Additionally, by sequentially turning the MYC gene on and off in these tumors in order to simulate the treatment of patients with multiple rounds of a molecularly targeted therapy, the investigators found that nearly every tumor eventually progressed to a state that was no longer dependent upon MYC for growth.


With these experiments, Chodosh and colleagues demonstrated that small numbers of breast cancer cells that remain following targeted therapy provide a means for cancers to escape and eventually recur. When tumors shrink in response to therapy, they leave residual cells that ultimately give rise to recurrences. Furthermore, if the targeted oncogene becomes reactivated in those cells, they grow into full-blown tumors very quickly. "Any way you look at it, when physicians apply a selective pressure to a tumor by blocking an oncogenic pathway, cells escape," says Chodosh. "They find a back door and progress to a more aggressive state that becomes independent of that pathway."

Chodosh concludes that the type of genetically engineered mouse models used in these MYC studies yield results that are very similar to what is observed in patients and that molecular therapies will likely need to be applied chronically to prevent the regrowth of residual tumor cells that remain after therapy. He further emphasizes that molecularly targeted therapies will need to be combined with agents that target secondary pathways of tumor escape in order to achieve lasting cures.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Health and Medicine:

nachricht Minimising risks of transplants
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht FAU researchers demonstrate that an oxygen sensor in the body reduces inflammation
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

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...

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

Stiffness matters

22.02.2018 | Life Sciences

Magnetic field traces gas and dust swirling around supermassive black hole

22.02.2018 | Physics and Astronomy

First evidence of surprising ocean warming around Galápagos corals

22.02.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>