Improving breast cancer chemo by testing patient's tumors in a dish

October 28, 2014

One of the tragic realities of cancer is that the drugs used to treat it are highly toxic and their effectiveness varies unpredictably from patient to patient. However, a new "tumor-in-a-dish" technology is poised to change this reality by rapidly assessing how effective specific anti-cancer cocktails will be on an individual's cancer before chemotherapy begins.

A team of biomedical engineers at Vanderbilt University headed by Assistant Professor Melissa Skala has developed the technique, which uses fluorescence imaging to monitor the response of three-dimensional chunks of tumors removed from patients and exposed to different anti-cancer drugs.

In an article published last month by the journal Cancer Research the engineers describe applying the technique to the three major forms of breast cancer. They report that the test can detect significant drops in the metabolic activity levels of all three types of tumors within 72 hours when exposed to an effective drug whereas tumors that were resistant to a drug show no change.

One in eight women in the United States will develop invasive breast cancer in their lifetime. Breast cancer kills about 40,000 women annually making it the second leading cause of cancer death in women - exceeded only by lung cancer, according to the American Cancer Society.

When breast cancer is diagnosed, the drug regimen that the patient receives is based primarily on the results of a biopsy that is used to identify the type of tumor she has. The effectiveness of the initial treatment is assessed after two to three months by determining whether the tumors are shrinking or continuing to grow.

According to several studies, in more than 100,000 cases each year the breast cancers do not respond to the standard drugs, either initially or after repeated doses. As a result, 33 to 43 percent of patients must be switched to different drug regimens.

"Right now it's a guessing game," said Skala. "We hope that our test will significantly improve the odds of survival of breast cancer patients by allowing doctors to identify the most effective but least toxic form of chemotherapy for each individual patient before the treatment begins."

According to Skala, more than 100 different anticancer drugs are currently available, but only ten to 15 are used regularly.

The new "tumor in a dish" method begins by taking the cancerous tissue removed during surgery or biopsy, cutting it up into small pieces and putting them in a special collagen gel that maintains them as "organoids" that retain the three-dimensional structure of the original tumor and include supporting cells from the tumor's environment.

The traditional method of culturing tumor cells produces a single layer of cells that behave much differently from the original tumor. So cancer researchers have developed methods for culturing three-dimensional tumor organoids that mimic the behavior of the original tumors so they can study how they grow.

"This is the first time the 3-D culturing method has been used to predict the effectiveness of different drugs on tumors from individual patients," said graduate student Alex Walsh, who has played a key role in developing the test.

The researchers use a technique called "optical metabolic imaging" to measure the activity level of the organoids. The technique uses a laser that is tuned to the frequencies that cause two key enzymes in the cells to fluoresce. Measuring the variations in the intensity of the resulting fluorescence provides a "dynamic readout of cellular metabolism" which is a sensitive biomarker of drug response. Their tests show responses to drug exposures within 24 hours.

"We hit the tumor with a punch and see how it responds," said Skala, "It is cheap and fast and adaptable to high-throughput screening so it can be used to test dozens of drugs or drug combinations at the same time."

The test also measures the responses of all the individual cells in the organoid. This is important because tumors are not all alike and some types of tumor cells may respond differently to a specific drug than others, Skala pointed out. If a given drug cocktail kills 90 percent of the cancer cells but doesn't affect the remaining 10 percent, the resistant tumor cells can take over and cause the tumor to grow back.

"Our test should make it possible to find drug combinations that kill ALL the cancerous cells in a tumor," Skala said.

So far they have tested the method extensively in mice and with six samples of human tumors using four anticancer drugs commonly used to treat breast cancer and two experimental drugs.

"The next step is to test tumors from more human patients and see how the results compare to the response that the patients have to chemotherapy," said Walsh.

If these experiments validate the test results, as the researchers expect, then they estimate that it could become available clinically within 5-10 years.

After validating the test for breast cancer, they intend to see how well it works with pancreatic cancer. Although pancreatic cancer is relatively rare, accounting for about 3 percent of all the cases of cancer in the United States, it has an extremely high mortality rate so it accounts for about 7 percent of all cancer deaths.
-end-
Assistant Professor of Cancer Biology Rebecca Cook, Associate Professor of Pathology, Microbiology and Immunology Melinda Sanders and Professor of Medicine and Cancer Biology Carlos Arteaga from Vanderbilt University Medical Center along with Luigi Aurisicchio from Takis Biotech in Rome, Italy and Gennaro Ciliberto from the IRCCS National Cancer Institute in Naples, Italy also contributed to the research.

The research is supported by National Science Foundation grant DGE-0909667, Department of Defense grant BC1219981, National Institutes of Health grant R00-CA142888, National Cancer Institute grant P50-CA098131 and Vanderbilt University.

Visit Research News @ Vanderbilt for more research news from Vanderbilt. [Media Note: Vanderbilt has a 24/7 TV and radio studio with a dedicated fiber optic line and ISDN line. Use of the TV studio with Vanderbilt experts is free, except for reserving fiber time.]

Vanderbilt University

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.