New method may allow personalized clinical trial for cancer therapies

August 13, 2012, Vanderbilt University Medical Center

A new tool to observe cell behavior has revealed surprising clues about how cancer cells respond to therapy – and may offer a way to further refine personalized cancer treatments.

The approach, developed by investigators at Vanderbilt-Ingram Cancer Center, shows that erlotinib – a targeted therapy that acts on a growth factor receptor mutated in some lung, brain and other cancers – doesn't simply kill as was previously assumed. The drug also causes some to go into a non-dividing (quiescent) state or to slow down their rate of division. This variability in cell response to the drug may be involved in cancer recurrence and drug resistance, the authors suggest.

The new tool, reported Aug. 12 in Nature Methods, may offer ways to improve personalized cancer therapy by predicting tumor response and testing combinations of targeted therapies in an individual patient's tumor.

In the personalized approach to cancer treatment, a patient's tumor is analyzed for a set of mutations to which there are matching drugs that act on those mutations.

This approach has worked rather well for many cancers that carry specific mutations, said senior author Vito Quaranta, M.D., professor of Cancer Biology.

"The genetics is well understood, the clinical effect is understood and the chemistry behind the therapy is understood. But there is a missing piece," said Quaranta. "Believe it or not, what is actually not understood is how cells respond to these drugs, what is actually happening."

The prevailing view has been that targeted therapies kill all the cells harboring a particular mutation.

But even if the tumor is composed entirely of genetically identical cells – which is unlikely – a drug will not affect all cells the same way, Quaranta explained.

"Some of these cells may die, some may just stop dividing and sit there (called quiescence), and some may keep dividing, but more slowly."

However, no current tests can provide an accurate, detailed picture of needed to understand tumor response to drugs.

So, the investigators, led by first author Darren Tyson, Ph.D., research assistant professor of Biology, combined powerful automated, time-lapse microscopy with analytical tools and software they developed.

Using these techniques, they could capture the behavior of lung every six to 10 minutes for up to 10 days.

As they expected, the targeted therapy erlotinib killed some cells, while others became quiescent. They observed that the drug even affected genetically identical cells (cells that arose from the same parental cell) differently.

"These cells are clearly genetically identical, as identical as they can possibly be because one cell just divided into two, but you get completely different responses: one dies and the other one doesn't," said Tyson. "This suggests that there are other things besides genetics that have to be taken into account."

What those other factors are remains unclear, but the investigators are conducting follow- up experiments to determine what might underlie this differential response.

"And presumably, it is those (quiescent) cells that ultimately result in tumor recurrence," said Tyson.

Quaranta and colleagues hope to take the technology into small clinical trials to test whether it can predict a patient's response to therapy.

"We think that we might be able to forecast what the response is going to be," Quaranta said. "We can take samples from the tumor, subject them to this assay, and since we're looking at response over time, we will have a rate of response."

This could tell oncologists how long a patient's tumor will respond to a given therapy before it recurs. Such information could also help determine which patients will require more aggressive treatment – and Quaranta believes the assay will be able to test combinations of drugs on a patient's tumor cells to find the right combination to induce a response.

"We're hoping that this assay – or some implementation of this assay – will eventually work like a personalized clinical trial," Quaranta said.

Explore further: Researchers ID cancer gene-drug combinations ripe for precision medicine

Related Stories

Researchers ID cancer gene-drug combinations ripe for precision medicine

July 21, 2016
In an effort to expand the number of cancer gene mutations that can be specifically targeted with personalized therapies, researchers at University of California San Diego School of Medicine and Moores Cancer Center looked ...

Outdated assessment of treatment response makes good cancer drugs look bad

August 9, 2016
Tumor shrinkage is not the only measure of a successful anti-cancer therapy. A University of Colorado Cancer Center article published in the journal Frontiers in Oncology describes a promising alternative: metabolic imaging. ...

Current cancer drug discovery method flawed, study finds

May 2, 2016
The primary method used to test compounds for anti-cancer activity in cells is flawed, Vanderbilt University researchers report May 2 in Nature Methods. The findings cast doubt on methods used by the entire scientific enterprise ...

Breast cancer tumor-initiating cells use mTOR signaling to recruit suppressor cells to promote tumor

May 16, 2016
Not every breast cancer tumor follows the same path to grow. Some tumors have the assistance of myeloid-derived suppressor cells (MDSCs), a diverse type of immune cell involved in the suppression of the body's response against ...

Research suggests new tool for cancer treatment based on cell type

August 11, 2016
A new tumor model has been shown to predict how certain types of cancer cells react differently to a commonly used chemotherapy drug, a potential tool for "precision medicine," in which drug treatment is tailored to individual ...

'Precision' cancer treatment may extend lives

May 19, 2016
(HealthDay)—"Precision" cancer treatment that's guided by genetic clues from the patient's own tumor appears to outperform traditional chemotherapy, a new research review finds.

Recommended for you

Researchers create a drug to extend the lives of men with prostate cancer

March 16, 2018
Fifteen years ago, Michael Jung was already an eminent scientist when his wife asked him a question that would change his career, and extend the lives of many men with a particularly lethal form of prostate cancer.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...

Joint supplement speeds melanoma cell growth

March 15, 2018
Chondroitin sulfate, a dietary supplement taken to strengthen joints, can speed the growth of a type of melanoma, according to experiments conducted in cell culture and mouse models.

Improved capture of cancer cells in blood could help track disease

March 15, 2018
Tumor cells circulating throughout the body in blood vessels have long been feared as harbingers of metastasizing cancer - even though most free-floating cancer cells will not go on to establish a new tumor.

Area surrounding a tumor impacts how breast cancer cells grow

March 14, 2018
Cancer is typically thought of as a tumor that needs to be removed or an area that needs to be treated with radiation or chemotherapy. As a physicist and cancer researcher, Joe Gray, Ph.D., thinks differently.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.