First genetic-based tool to detect circulating cancer cells in blood

November 17, 2014

Metastasis is bad news for cancer patients. Northwestern University scientists now have demonstrated a simple but powerful tool that can detect live cancer cells in the bloodstream, potentially long before the cells could settle somewhere in the body and form a dangerous tumor.

The NanoFlare technology is the first genetic-based approach that is able to detect live circulating tumor cells out of the complex matrix that is human blood -- no easy feat. In a breast cancer study, the NanoFlares easily entered cells and lit up the cell if a biomarker target was present, even if only a trace amount. The NanoFlares are tiny spherical nucleic acids with gold nanoparticle cores outfitted with single-stranded DNA "flares."

"This technology has the potential to profoundly change the way breast cancer in particular and cancers in general are both studied and treated," said Chad A. Mirkin, a nanomedicine expert and a corresponding author of the study.

Mirkin's colleagues C. Shad Thaxton, M.D., and Chonghui Cheng, M.D., both of Northwestern University Feinberg School of Medicine, are also corresponding authors.

The research team, in a paper to be published the week of Nov. 17 by the Proceedings of the National Academy of Sciences (PNAS), reports two key innovations: "Cancers are very genetically diverse, and it's important to know what cancer subtype a patient has," Mirkin said. "Now you can think about collecting a patient's cells and studying how those cells respond to different therapies. The way a patient responds to treatment depends on the genetic makeup of the cancer."

Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering.

A NanoFlare is designed to recognize a specific genetic code snippet associated with a cancer. The core nanoparticle, only 13 nanometers in diameter, enters cells, and the NanoFlare seeks its target. If the genetic target is present in the cell, the NanoFlare binds to it and the reporter "flare" is released to produce a fluorescent signal. The researchers then can isolate those cells.

"The NanoFlare turns on a light in the cancer cells you are looking for," said Thaxton, an assistant professor of urology at Feinberg. "That the NanoFlares are effective in the complex matrix of human blood is a great technical advance. We can find small numbers of cancer cells in blood, which really is like searching for a needle in a haystack."

Once they identified the cancer cells, the researchers were able to separate them from normal cells. This ability to isolate, culture and grow the cancer cells will allow researchers to zero in on the cancer cells that matter to the health of the patient. Most circulating tumor cells may not metastasize, and analysis of the cancer cells could identify those that will.

"This could lead to personalized therapy where we can look at how an individual's cells respond to different therapeutic cocktails," said Mirkin, whose lab developed NanoFlares in 2007.

In the study, the genetic targets were messenger RNA (mRNA) that code for certain proteins known to be biomarkers for aggressive breast cancer cells.

The research team first used the blood of healthy individuals, spiking some of the blood with living breast cancer cells to see if the NanoFlares could detect them. (Unspiked blood was used as a control.)

Cheng, an assistant professor of medicine in hematology/oncology at Feinberg, provided the cell lines and NanoFlare targets the researchers used to model blood samples taken from breast cancer patients.

The research team tested four different NanoFlares, each with a different genetic target relevant to breast cancer metastasis. The technology successfully detected the cancer cells with less than 1 percent incidence of false-negative results.

Currently, in another study, the researchers are focused on detecting circulating tumor cells in the blood of patients with a diagnosis of breast cancer.

"When it comes to detecting and treating cancer, the mantra is the earlier, the better," Thaxton said. "This technology may enable us to better detect circulating cancer cells and provides another tool to add to the toolkit of cancer diagnosis."
-end-
Mirkin, Thaxton and Cheng are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

The title of the paper is "NanoFlares for the detection, isolation, and culture of live tumor cells from human blood."

In addition to Mirkin, Thaxton and Cheng, other authors of the paper are Tiffany L. Halo (co-first author), Kaylin M. McMahon (co-first author), Nicholas L. Angeloni, Yilin Xu, Wei Wang and Alyssa B. Chinen, all from Northwestern University, and Vincent L. Cryns, Dmitry Malin and Elena Strekalova, from the University of Wisconsin School of Medicine and Public Health.

Editor's note: Chad Mirkin and Shad Thaxton have interest in AuraSense, a biotechnology company that licensed the NanoFlare technology from Northwestern University. Mirkin and Thaxton are co-founders of the company.

Northwestern 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.