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 On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

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: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>