Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Transforming cancer treatment

12.07.2012
Multidrug strategy emerges from new research
A Harvard researcher studying the evolution of drug resistance in cancer says that, in a few decades, “many, many cancers could be manageable.”

“Many people are dying needlessly of cancer, and this research may offer a new strategy in that battle,” said Martin Nowak, a professor of mathematics and of biology and director of the Program for Evolutionary Dynamics. “One hundred years ago, many people died of bacterial infections. Now, we have treatment for such infections — those people don’t have to die. I believe we are approaching a similar point with cancer.”

Nowak is one of several co-authors of a paper, published in Nature on June 28, that details how resistance to targeted drug therapy emerges in colorectal cancers and describes a multidrug approach to treatment that could make many cancers manageable, if not curable.

The key, Nowak’s research suggests, is to change the way clinicians battle the disease.

Physicians and researchers in recent years have increasingly turned to “targeted therapies” — drugs that combat cancer by interrupting its ability to grow and spread — rather than traditional chemotherapy, but such treatment is far from perfect. Most targeted therapies are effective for only a few months before the cancer evolves resistance to the drugs.

The culprit in the colon cancer treatment examined in the Nature paper is the KRAS gene, which is responsible for producing a protein to regulate cell division. When activated, the gene helps cancer cells develop resistance to targeted-therapy drugs, effectively making the treatment useless.

To better understand what role the KRAS gene plays in drug resistance, a team of researchers led by Bert Vogelstein, the Clayton Professor of Oncology and Pathology at the Johns Hopkins Kimmel Cancer Center, launched a study that began by testing patients to determine if the KRAS gene was activated in their tumors. Patients without an activated KRAS gene underwent a normal round of targeted therapy treatment, and the initial results — as expected — were successful. Tests performed after the treatment broke down, however, showed a surprising result: The KRAS gene had been activated.

As part of the research, Vogelstein’s team analyzed a handful of mutations that can lead to the activation of the KRAS gene. To help interpret those results, they turned to Nowak’s team, including mathematicians Benjamin Allen, a postdoctoral fellow in mathematical biology, and Ivana Bozic, a postdoctoral fellow in mathematics.

Analyzing the clinical results, Allen and Bozic were able to mathematically describe the exponential growth of the cancer and determine whether the mutation that led to drug resistance was pre-existing, or whether it occurred after treatment began. Their model was able to predict, with surprising accuracy, the window of time from when the drug is first administered to when resistance arises and the drug begins to fail.

“By looking at their results mathematically, we were able to determine conclusively that the resistance was already there, so the therapy was doomed from the start,” Allen said. “That had been an unresolved question before this study. Clinicians were finding that these kinds of therapies typically don’t work for longer than six months, and our finding provides an explanation for why that failure occurs.”

Put simply, Nowak said, the findings suggest that, of the billions of cancer cells that exist in a patient, only a tiny percentage — about one in a million — are resistant to drugs used in targeted therapy. When treatment starts, the nonresistant cells are wiped out. The few resistant cells, however, quickly repopulate the cancer, causing the treatment to fail.

“Whether you have resistance prior to the start of treatment was one of the large, outstanding questions associated with this type of treatment,” Bozic said. “Our study offers a quantitative understanding of how resistance evolves, and shows that, because resistance is there at the start, the single-drug therapy won’t work.”

The answer, Nowak said, is simple: Rather than the one drug used in targeted therapy, treatments must involve at least two drugs.

Nowak isn’t new to such strategies. In 1995 he participated in a study, also published in Nature, that focused on the rapid evolution of drug resistance in HIV. The result of that study, he said, was the development of the drug “cocktail” many HIV-positive patients use to help manage the disease.

Such a plan, however, isn’t without challenges.

The treatment must be tailored to the patient, and must be based on the genetic makeup of the patient’s cancer. Perhaps even more importantly, Nowak said, the two drugs used simultaneously must not overlap: If a single mutation allows the cancer to become resistant to both drugs, the treatment will fail just as the single-drug therapy does.

Nowak estimated that hundreds of drugs might be needed to address all the possible treatment variations. The challenge in the near term, he said, is to develop those drugs.

“This will be the main avenue for research into cancer treatment, I think, for the next decade and beyond,” Nowak said. “As more and more drugs are developed for targeted therapy, I think we will see a revolution in the treatment of cancer.”

Peter Reuell | EurekAlert!
Further information:
http://www.harvard.edu
http://news.harvard.edu/gazette/story/2012/07/transforming-cancer-treatment/

More articles from Life Sciences:

nachricht Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo

nachricht Full of hot air and proud of it
18.04.2018 | University of Pittsburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Diamond-like carbon is formed differently to what was believed -- machine learning enables development of new model

19.04.2018 | Materials Sciences

Electromagnetic wizardry: Wireless power transfer enhanced by backward signal

19.04.2018 | Physics and Astronomy

Ultrafast electron oscillation and dephasing monitored by attosecond light source

19.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>