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 More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

More genes are active in high-performance maize

19.01.2018 | Life Sciences

How plants see light

19.01.2018 | Life Sciences

Artificial agent designs quantum experiments

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>