Reversing Resistance to Tamoxifen
Blocking a particular growth factor appears to increase tamoxifen's ability to fight breast cancer cells that have become resistant to the drug, suggests a new study. However, it is not yet clear if such a strategy will work in women with breast cancer that has already become resistant to tamoxifen treatment.
Breast cancer cells that have estrogen receptors on their surface-between 40% to 60% of breast cancers-usually can be treated with tamoxifen, a drug that blocks the growth-promoting effects of estrogen. However, some cells produce high levels of "transforming growth factor-beta" (TGF-b), a naturally occurring cell growth regulator, and tend to be resistant to tamoxifen.
In the study, published in the Journal of the National Cancer Institute, one breed of mice did not grow tumors if researchers treated them with tamoxifen in combination with injections of an antibody that blocked TGF-b. Such mice normally develop tumors when injected with breast cancer cells that overproduce TGF-b and are resistant to tamoxifen treatment, said lead author Dr. Carlos Arteaga of Vanderbilt University in Nashville, TN.
SOURCE: Journal of the National Cancer Institute
Human Chromosome Stops Cancer Growth
Scientists in the United Kingdom report that the addition of human chromosome 3 to a line of breast cancer cells completely stops tumor growth. According to the study published in the Journal of the National Cancer Institute, "the search is now on for anticancer drugs that can produce the same effect."
Normal human cells stop dividing and growing after a limited number of cell divisions. But most tumor cells continue to divide indefinitely. The enzyme telomerase is responsible in part for this cell immortality. Nearly all normal cells lack telomerase activity, while nearly all tumor cells show high levels of enzyme activity.
Dr. Andrew Cuthbert and colleagues at Brunel University in Uxbridge, UK, studied cell lines of breast cancer called 21NT. The researchers then introduced either chromosome 3,8,12 or 20 to the cell lines. Only the cells that received chromosome 3 showed complete growth arrest. There was also a 98 percent dip in telomerase activity. Other cell lines continued to grow as before.
The scientists hope that their finding may open the door to a new approach to the treatment of cancer. A telomerase inhibitor drug "might lead to novel therapeutic strategies," they wrote.
The finding could lead to "a new way to manage cancer," added Dr. Jerry Shay of the University of Texas Southwestern Medical Center in an accompanying editorial. Instead of killing cancer cells (and many normal cells) outright, a telomere repressor would result in eventual cell death.
Because cancer cells have shorter telomeres than normal cells, such an agent might have less toxicity than many chemotherapy agents used today. "The challenge is to find out how to make our cancer cells age and stop dividing, and our aging but healthy cells continue to divide," Shay said.
SOURCE: Journal of the National Cancer Institute
Putting Salmonella to Good Use
A dreaded cause of food poisoning, salmonella, might actually have a good use, according to researchers at Yale University. A new report shows the bacteria appears to fight cancer.
"When we administer this to mice that have tumors, there is a greater than 90 percent suppression of tumor growth," said David Bermudes of Vion Pharmaceuticals, which teamed up with Yale to conduct the research.
Scientists infected the mice with human cancer tumors. Then they injected genetically engineered salmonella into the bloodstream of the animals. The salmonella bacteria sought out the tumors, multiplied inside them and slowed the growth of the cancer. "We can now significantly prolong the life of mice with melanoma by injecting them with our attenuated bacteria," said Yale's Dr. John Paweleck.
Scientists aren't exactly sure why salmonella seems to work. Yet they plan on approaching the Federal Drug Administration to start human trials sometime in 1999. But giving salmonella to humans is a risky proposition. What if the cancer is treated, but the patients die of food poisoning?
That's why the Yale and Vion researchers are so impressed with this genetically altered strain of salmonella. The lab animals in the study did not get sick. "What we've been able to do is to remove toxic consequences of salmonella yet retain their beneficial properties of specifically targeting tumors and suppressing tumor growth," Bermudes said.
Unaltered or "wild" type salmonella kills all kinds of cells; the re-engineered strain targets only tumor cells. While as few as 10 natural salmonella bacteria are enough to kill a mouse, mice injected with 10 million cells of the mutant strain showed no signs of infection.
Despite the discovery, cancer experts urge patients to remember that salmonella found in food won't fight cancer. "This is a very special bacteria. It's not the one they are going to get from raw chicken," Willis said. "It's a laboratory strain that's been very carefully genetically engineered not to cause them any harm."
Kinder Chemicals for Cancer Therapy
A team of scientists have reported a discovery that could lead to a cancer treatment more gentle on the human body than traditional chemotherapy. The team, based at the University of California at Los Angeles, said it has discovered a family of chemicals that could allow doctors to use "boron neutron capture therapy" on cancer patients.
The UCLA scientists said the new cancer therapy would be less harsh on the body than traditional chemotherapy because it targets only cancer cells and kills them with nuclear fission instead of chemicals that poison the body. The team's findings were published in the journal Proceedings of the National Academy of Sciences.
"It would be selective for cancer cells and therefore the therapy itself would be much less debilitating for the patient," said Frederick Hawthorne, a UCLA chemist who led the research team. "If (the therapy) lives up to expectations, it will be much more comfortable for the patient than chemotherapy or other types of radiation therapy."
Hawthorne said it was too early to tell if the boron therapy, which faces several years of clinical trials before it could be made available to the public, would be more effective than current cancer treatments.
The concept of using boron-based compounds to fight cancer has been around since the 1930s, when scientists discovered that those compounds accumulate in cancerous tumors. But the newly discovered family of chemicals is the most effective so far at delivering the boron into the nucleus of the cancer cells, Hawthorne said.
Once there, the boron is "activated" by exposing the cancer cells to a beam of neutrons, producing nuclear fission that destroys the cells' DNA. "Boron can be considered something like a land mine, because it's just sitting there until something comes along and steps on it," Hawthorne said. "In this case, that something is the neutron. And when it goes off, it destroys whatever happens to be around it."
That capability could make it more attractive than chemotherapy, which damages healthy cells as it kills cancer cells, often leaving the patient ill in the process. "What all these methods would love to do is cure cancer without disturbing normal tissue nearby," Hawthorne said. "This particular method would allow one to do just that."
SOURCE: Proceedings of the National Academy of Sciences
Closing in on Cancer Vaccines
The first of several experimental cancer vaccines may be considered by the Food and Drug administration for approval sometime this year, a step toward fulfilling scientists' longstanding dreams of enlisting the body's own immune system to fight malignant tumors.
From breast, prostate and colon cancers to malignant melanoma, scientists are manipulating tumor cells to design treatments that will target the patient's cancer much as a vaccine provokes an immune response to infection.
Rather than prevent disease, these cancer vaccines are being used to treat patients, by mounting a specific immunological defense against malignant cells in the body. "I think there is real progress being made," said Dr. Paul Chapman of Memorial Sloan-Kettering Cancer Center. "A lot of teams are just going crazy with different tumor systems-breast, prostate and others-to identify appropriate targets" for cancer vaccines.
Researchers say they expect the pace of cancer vaccine development to accelerate over the next decade as they continue to refine their understanding of why malignant cells develop and how the immune system recognizes cancer.
SOURCE: The Washington Post
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