Experts discover how ‘cancer’ hibernates

UVA reveals how cancer-causing virus clings to human DNA

A health worker prepares an Ebola vaccine to administer to health workers during a vaccination campaign in Mbandaka, Congo on May 21. (AP)

PARIS, May 23, (Agencies): Scientists have identified the mechanism that allows breast cancer cells to lie dormant in other parts of the body only to reemerge years later with lethal force, according to a study published Tuesday.

In experiments with human cells and live mice, researchers showed that disabling the mechanism — with drugs or gene manipulation — crippled the cancer cells and inhibited their capacity to spread.

The discovery, reported in the journal Nature Communications, provides a promising target for the development of breast cancer therapies, the study said.

Some 90 percent of breast cancer deaths occur with metastasis, when the disease moves to other organs or parts of the body.

Scientists have struggled to understand how cancer cells manage to remain hidden — sometimes for decades — and what, exactly, triggers their reawakening.

“Our results suggest that breast cancer cells can survive, undetected, in patients for long periods by using a cellular process known as autophagy,” said co-author Kent Hunter, a researcher at the National Cancer Institute (NCI) in Bethesda, Maryland.

Autophagy occurs when any cell — healthy or cancerous — reshuffles internal components to survive in a stressful and nutrient-poor environment. This allows the cell to partially shut down, entering a state similar to hibernation.

The findings help explain why current treatments so often fail to root out breast cancer cells that remain after surgery and chemotherapy.

“Many of the traditional anti-cancer drugs are designed to target dividing cells,” said Hunter.

Resistant

“Dormant cells, however, are not actively or frequently dividing, and are therefore thought to be resistant to these types of drugs.”

The fact that they are hiding elsewhere in the body also helps the cells escape localised treatments such as radiation.

In an experiment, researchers led by Hunter’s colleague Laura VeraRamirez injected dormant breast cancer cells into mice.

Half the animals were given a drug that inhibits autophagy, while the others received a placebo or “dummy” drug.

In a second experiment, they altered a gene that controls autophagy.

Both approaches “significantly” decreased survival of the cancer cells and limited their spread, the study concluded.

Without recourse to autophagy, the cancer cells accumulated toxic matter and damage to their mitochondria, the energy-producing units of cells.

The road to a viable treatment will be long, said Hunter. A clinical trial will have to be performed to determine whether the treatment would work in human patients.

It is also unknown whether the findings apply to other types of cancer, he added.

Using a homemade, high-tech microscope, scientists at the University of Virginia School of Medicine have revealed how a cancer-causing virus anchors itself to our DNA. That discovery could pave the way for doctors to cure incurable diseases by flushing out viruses, including HPV and EpsteinBarr, that now permanently embed themselves in our cells.

“The reason we can’t get rid of these [viruses] is because we can’t figure out a way to get their DNA out of the nucleus, out of the cell,” explained UVA researcher Dean H. Kedes, MD, PhD. “They depend on this ‘tether’ to remain anchored to the DNA within our cells, and to remain attached even as the cells divide. This tether is a key factor to disrupt in devising a cure.”

Now that scientists can understand this vital infrastructure, they can work to disassemble it. “Without it,” Kedes noted, “the virus is going to lose its hold in the body. … Bad for the virus, but very good for the patient.”

Structure

The researchers used the microscope built by fellow investigator M. Mitchell Smith, PhD, to reveal the structure of the tether used by a virus called Kaposi’s sarcoma-associated herpesvirus (KSHV). Until now, such tethers have largely eluded scientists because they are so diabolically small, defying even the most high-tech approaches to determining their form. “We’re seeing things on the order of 8,000 times smaller than a human hair,” said Smith, who built UVA’s microscope piece-by-piece based on one pioneered in the Physics and Astronomy Department at the University of Maine.

Smith’s microscope is nothing like the simple light microscope seen in every high school biology class. It’s a stunning marriage of stainless steel and laser beams, looking much like an oversized sci-fi Erector set. It sits on a table that almost fills a small room.

“It’s a set of lasers, a bunch of optics that focus and filter the lasers,” Smith explained, gesturing to various components. “I’m trained as a molecular geneticist, not as an optical physicist … so we worked on it for maybe three years. But it’s continually a work in progress.”