'Energy blocker' kills big tumors in rats

October 14, 2004

Building on their earlier work, Johns Hopkins researchers have discovered that an apparently nontoxic cellular "energy blocker" can eradicate large liver tumors grown in rats. Six months to more than a year after treatment was stopped, the rats are still cancer free.

While the results are dramatic, clinical trials with the chemical, 3-bromopyruvate, are likely some years away, says the study's leader, Young Ko, Ph.D., assistant professor of radiology and biological chemistry. If tests in the lab continue to be promising, however, the chemical or one like it may become an option for treating advanced liver cancers and perhaps other tumors in people.

"Liver cancer usually isnt detected in people until its difficult or impossible to treat, and many other aggressive cancers spread to the liver, so we need more treatment options," says Peter Pedersen, Ph.D., professor of biological chemistry in the Institute for Basic Biomedical Sciences at Johns Hopkins. "The compound Dr. Ko tested in animals targets a fundamental process cancer cells need to survive, can kill big tumors, and appears so far to have little or no effect on normal tissues."

In fact, Ko says she hasn't been able to find a toxic dose of the compound, which blocks the two ways cancer cells make energy. In earlier experiments with rabbits with liver cancer, reported in 2002, no obvious toxic effects were seen, either. There is a patent pending on possible cancer applications of the compound.

While the details of normal cells' protection are still unclear, the scientists suggest cancer cells well-known appetite for sugar might be behind their demise. Ko, who first studied the compound as a graduate student at Washington State University in 1990 and initiated its study at Hopkins, has shown that it completely blocks cancer cells' conversion of sugar into usable energy, a process necessary to fuel the cells' functions and growth.

"We believe this is the first time that a drug has blocked both ways cancer cells make energy and are very happy that it seems so effective against advanced liver cancers," says Ko. "Usually researchers don't try to attack advanced cancers because success seems unlikely. But these are the very cancers we must learn to defeat if we are to win the war on cancer."

Sugar, or glucose, is brought into cells and converted into useable energy, a molecule called ATP, by either of two processes. Another product of this conversion, a molecule called lactate, is then taken out of the cell by specialized transporters.

But because cancer cells use so much more sugar and make so much more lactate than normal cells, the researchers suggest cancer cells may be riddled with more of the "two-way streets" that transport lactate. And because 3-bromopyruvate looks very similar to lactate, it might travel those same roads, sneaking into cancer cells like a Trojan horse, suggests Ko.

In her latest experiments, described in the Nov. 5 issue of Biochemical and Biophysical Research Communications and available online now, Ko found that treating rat liver cancer cells with 3-bromopyruvate halted the cells production of ATP within 30 minutes, and visual evidence of the cells' self-destruction was apparent almost immediately. Four times as much of the compound was necessary to begin decreasing ATP production in normal liver cells.

Turning to animal studies, Ko injected rat liver cancer cells into either the abdomen or the upper back of 33 rats. Nineteen of the animals received daily injections of the compound into the tumor site for five days or longer, which caused all of the cancers to disappear within four weeks. The rats otherwise appeared unaffected, although Ko will examine the animals when they are euthanized -- probably for old age. The 14 untreated animals that served as controls were euthanized within 10 days because of their tumors' rapid growth.

To be sure that the compound had completely eradicated the tumors in the treated animals, Ko and Pedersen collaborated with radiologist Martin Pomper, M.D., Ph.D., Yuchuan Wang, Ph.D., and James Fox. They used radioactive glucose to take PET scans of four of the rats and found that "hot spots" of high uptake disappeared within a few weeks of treatment. PET scans are commonly used to diagnose or stage cancers in people because of tumors' appetite for glucose.

Ko is now studying the compound's effects on human cancer cell lines in the lab, and will begin studying it in animal models of breast cancer shortly. The researchers also are planning to examine the compound's effects in an animal model of an aggressive non-liver cancer that spreads to the liver.
-end-
The research was funded by the National Cancer Institute and the Johns Hopkins Department of Radiology. Authors on the paper are Ko, Wang, Pomper, Pedersen, Barbara Smith, David Rini, Michael Torbenson and Joanne Hullihen, all of Johns Hopkins.

Media Contact: Joanna Downer or Diane Bovenkamp
410-614-5105; jdowner1@jhmi.edu
For Immediate Release: Thursday, Oct. 14, 2004

Note: An audio file of Peter Pedersen, Ph.D., discussing the success in treating advanced liver cancers in rats and two photographs showing a rat before and after treatment are available by contacting jdowner1@jhmi.edu. A photo is available at: http://www.hopkinsmedicine.org/Press_releases/2004/10_14_04.html

On the Web:

For this paper in BBRC: http://www.sciencedirect.com/science/journal/0006291X
For their July 2002 paper in Cancer Research: http://cancerres.aacrjournals.org/

Johns Hopkins Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and 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.