Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Findings Point to an “Off Switch” for Drug Resistance in Cancer

22.10.2014

Salk research indicates a potential mechanism for cancer cells’ adaptability.

Like a colony of bacteria or species of animals, cancer cells within a tumor must evolve to survive. A dose of chemotherapy may kill hundreds of thousands of cancer cells, for example, but a single cell with a unique mutation can survive and quickly generate a new batch of drug-resistant cells, making cancer hard to combat.


Salk Institute

From left: Yelena Dayn, Fernando Lopez-Diaz, Beverly Emerson

Now, scientists at the Salk Institute have uncovered details about how cancer is able to become drug resistant over time, a phenomenon that occurs because cancer cells within the same tumor aren’t identical—the cells have slight genetic variation, or diversity. The new work, published October 20 in PNAS, shows how variations in breast cancer cells’ RNA, the molecule that decodes genes and produces proteins, helps the cancer to evolve more quickly than previously thought. These new findings may potentially point to a “switch” to turn off this diversity—and thereby drug resistance—in cancer cells.

“It’s an inherent property of nature that in a community—whether it is people, bacteria or cells—a small number of members will likely survive different types of unanticipated environmental stress by maintaining diversity among its members,” says the senior author of the new work, Beverly Emerson, professor of Salk’s Regulatory Biology Laboratory and holder of the Edwin K. Hunter Chair. “Cancer co-ops this diversification strategy to foster drug resistance.”

Instead of looking at a single gene or pathway to target with cancer therapies, lead author Fernando Lopez-Diaz, Salk staff scientist, and the team aim to uncover the diversification “switch” by which cancer cells replicate but vary slightly from one another. Turning off this cellular process would strip cancer’s ability to survive drug treatment.

“Cancer isn’t one cell but it’s an ecosystem, a community of cells,” says Emerson. “This study begins the groundwork for potentially finding a way to understand and dial back cell diversity and adaptability during chemotherapy to decrease drug resistance.”

To uncover how groups of cancer cells achieve functional diversity (through RNA) to survive chemotherapy, Lopez-Diaz dosed dishes of human pre-cancer and metastatic breast cancer cells with the cancer drug paclitaxel for a week and then removed the drug for a few weeks, mimicking the treatment cycle for a cancer patient. Surviving cells—usually one or two out of millions—began to repopulate but with subtle changes in their RNA, presumably enabling them to survive future doses of the cancer drug.

By pushing the boundaries of bioinformatics, a collaboration led by Mei-Chong Wendy Lee and Nader Pourmand at the University of California, Santa Cruz charted more than 80,000 pieces of RNA per new cancer cell—typically, single-cell studies by other approaches look at hundreds or so RNA pieces to distinguish fairly different cells from one another. This unusually thorough list helped the researchers tease out subtle differences between generations of same cancer cells treated with chemotherapy and chart how the cancer cell community increased diversity among its members through RNA.

“We found an overwhelming return to diversity after chemotherapy treatment that couldn’t be explained by expected mechanisms,” says Lopez-Diaz. “There is something else going on here, a ‘philosopher’s stone’ to cancer cell diversity that we now know to look for.”

And when the team analyzed the gene expression profiles of the surviving cancer cell line, they were again surprised. “We thought they’d look like stressed cells with a few changes,” says Emerson. “Instead, after a few population doublings they go back to the normal gene expression pattern and rapidly reacquired drug sensitivity.” This adaptive behavior, Emerson speculates, lets the group of cancer cells prepare for the next unanticipated threat.

Another intriguing finding of the paper was that a high percentage of precancerous cells that underwent chemotherapy survived and proliferated, more so than either normal or cancerous cells. This led the pre-cancer cells to become more drug tolerant once they became a tumor. “The pre-cancer cells, when exposed to chemotherapy, evolved much faster and create a more drug-resistant state,” says Lopez-Diaz. “This and other findings can now be explored into greater detail using the knowledge and perspective we have gained here.”

Authors of the work include Beverly M. Emerson, Fernando J. Lopez-Diaz and Yelena Dayn at the Salk Institute; Nader Pourmand, Mei-Chong Wendy Lee, Shahid Yar Khan, Muhammad Akram Tariq, Amie J. Radenbaugh, and Hyunsung John Kim of the University of California, Santa Cruz; and Charles Joseph Vaske of Five3 Genomics.

Funding for the work includes support from the National Institutes of Health, the Chambers Medical Foundation, the GemCon Family Foundation and the Olive Tupper Foundation.

About the Salk Institute for Biological Studies: 
The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probes fundamental life science questions in a unique, collaborative, and creative environment. Focused both on discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.

Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, MD, the Institute is an independent nonprofit organization and architectural landmark.

Salk Communications | newswise
Further information:
http://www.salk.edu

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>