Cancer CarePoint Blog

Scientists Spot Factor in Cancer's Spread

Yahoo News summarizes research from the latest issue of Nature describing drugs that may interfere with cancer spreading to bones. Excerpts below.

Link: Scientists Spot Factor in Cancer's Spread - Yahoo! News

Researchers have identified a molecule that appears to play a critical part in how cancers spread to bones.

Although the experiments were done in mice, the Austrian researchers hope the finding will lead to new treatments that can keep cancers such as breast, prostate and skin cancer from spreading to bone.

They found that a protein in bone called RANKL communicates with a receptor in breast, prostate and skin cancer cells, telling them to migrate.

Fortunately, there's already an available drug designed to block RANKL activity. The researchers are hopeful that the drug might also prevent cancers from spreading to bone.

Their report appears in the March 30 issue of Nature.

In its study, Penninger's team studied bone metastases in a mouse model of skin cancer. They gave some animals a drug called osteoprotegerin (OPG), known to inhibit RANKL.

The mice treated with OPG had fewer tumors in their bones compared with the untreated mice. In mice treated with OPG, there was significantly less spread of cancer into bones and vertebrae. And, unlike the untreated mice, none of the OPG-treated mice developed paralysis. However, the spread of cancer into other organs was not slowed in mice treated with OPG, the researchers found.

An estimated one million Americans with tumors develop bone metastases every year, and these metastases sometimes trigger massive pain, Penninger said. "If we are correct, one might be able to interfere with metastases, and with this [drug] might allow women with breast cancer, for instance, to have a decent life with less metastases and less cancer pain," he added.

Penninger stressed, however, that these findings are based on mouse studies, which don't always translate to humans.

One expert thinks these findings shed light on how cancer cells spread to bone.

For more on metastatic cancer, visit the U.S. National Cancer Institute.

Studies link cancer, inflammatory disease

Science Blog reports on research from MIT that links cancer and inflammatory disease. Excerpts below.

Link: Studies link cancer, inflammatory disease

The biological processes underlying diseases such as rheumatoid arthritis and cancer are fundamentally linked, and should be linked in how they are treated with drugs, a series of MIT studies indicates.

Key to the work: The researchers applied an engineering approach to cell biology, using mathematical and numerical tools normally associated with the former discipline.

In a series of three papers, the latest of which appeared in the March 24 issue of Cell, Professors Douglas A. Lauffenburger, Peter K. Sorger and Michael B. Yaffe, all members of MIT's Center for Cancer Research, led a team of scientists and engineers in looking at how cells make life-or-death decisions. Understanding what tips a cell toward survival or death is key to treating diseases and fighting cancer through radiation, drug therapy and chemotherapy.

The researchers looked at tumor necrosis factor (TNF), a substance produced by the immune system that promotes cell death, and two prosurvival hormones, epidermal growth factor (EGF) and insulin. TNF and EGF induce conflicting prosurvival and prodeath signals, and the "crosstalk" between these signals is not well understood. The MIT studies provide the first big picture of how these two key factors interact in time and space.

The studies uncovered a surprising link between inflammatory diseases and cancer that may change how these diseases are treated in the future.

Researchers have been exploring ways to use drugs in combination to increase their therapeutic value in fighting tumors. The results of the three MIT studies have implications for how two classes of drugs involving TNF and EGF affect common biological processes in the body.

This work is supported by the National Institutes of Health and the Whitaker Foundation.

From MIT

Promising Brain Tumor Vaccine

ABC News reports on a brain tumor treatment being tested in San Francisco using vaccines created from an individual tumor's healthy protein. Excerpts below.

Link: ABC News: Promising Brain Tumor Vaccine

Some San Francisco surgeons are using brain tumors to create special vaccines that they believe will extend the lives of the same patients those tumors are killing.

Some consider it a miraculous experiment, while others argue that it's too good to be true. But retired police Officer Barbara Hammerman calls it her last resort. At 46, she has lost her vision because of her brain tumor.

Hammerman is not alone. One in 174 men and women will be diagnosed with cancer of the brain and other nervous system during their lifetime, according to the American Cancer Society.

Some San Francisco surgeons are using brain tumors to create special vaccines that they believe will extend the lives of the same patients those tumors are killing.

Some consider it a miraculous experiment, while others argue that it's too good to be true. But retired police Officer Barbara Hammerman calls it her last resort. At 46, she has lost her vision because of her brain tumor.

Hammerman survived those nine months, but more tumors appeared. She received new hope when she met neurosurgeon Andrew Parsa at the University of California, San Francisco.

Parsa is running a clinical trial with 60 patients and a few other surgeons.

They send brain tumors to a biotech company called Antigenics where vaccines are created from an individual tumor's healthy protein, then injected back into the same patient.

The Food and Drug Administration has approved the clinical trials funded by the American Brain Tumor Association, but is still waiting to approve the actual treatment.

New 'Litmus Test' Could Aid Discovery Of Anti-cancer Drugs

ScienceDaily describes colorimetric screening research from Northwestern Univerity that might be used to identify anti-cancer drugs quickly. Excerpts below.

Link: ScienceDaily: New 'Litmus Test' Could Aid Discovery Of Anti-cancer Drugs

Using the unusual color properties of gold at the nanoscale, scientists at Northwestern University have developed a "litmus test" for DNA and small molecule binding that eventually could be used by pharmaceutical companies to rapidly identify promising candidates for new anti-cancer drugs.

The detection system, called colorimetric screening, can be used to detect a variety of targets, such as DNA, small molecules and proteins, that bind to DNA, and the strength of the bond is indicated by a simple color change.

In a paper reported online today (March 28) by the Journal of the American Chemical Society (JACS), the research team used the colorimetric method to screen for molecules that can facilitate the formation of a special form of DNA called a triple helix.

A certain DNA sequence might be linked to colon cancer, for example, and the proteins expressed by that DNA produce cancer cells. By identifying a triplex binder or small molecule that binds effectively to that particular DNA sequence, a drug can be developed that shuts down protein production and stops cancer cells from proliferating.

Their next step, said Mirkin, is to challenge the research community to provide libraries of triplex binders and small molecules for his research teams to test. Any interaction with DNA, whether it be with small molecules, proteins or other DNA, can be identified by the colorimetric method. "We want to identify the real winners," said Mirkin.

Pain killer does number on breast cancer cells

Science Blog describes Ohio State University research that suggests that a pain-killing drug, nimesulide, stops the production of the enzyme implicated in estrogen-dependent breast cancer. Excerpts below.

Link: Pain killer does number on breast cancer cells

A pain–killing medication appears to halt the production of an enzyme that is key to a common form of breast cancer, a new study using tissue cultures suggests.

The drug is called nimesulide. In laboratory experiments on breast cancer cells, scientists found that derivatives of nimesulide stopped the production of aromatase, the enzyme implicated in estrogen-dependent breast cancer. This form of breast cancer is the most common kind of breast cancer in postmenopausal women.

Aromatase converts hormones called androgens into estrogens, such as the hormone estradiol. Estrogen is a powerful mitogen – an agent that causes cells to divide, and too much estrogen can cause cells to divide too quickly.

While many women with estrogen-dependent breast cancer take aromatase inhibitors to control their disease, the problem is that the current inhibitor drugs halt estrogen production throughout the body, said Robert Brueggemeier, a study co-author and a professor of medicinal chemistry and pharmacognosy and dean of the College of Pharmacy at Ohio State University.

From Ohio State University

Imaging Technology Helps Identify Esophageal Cancer Patients Who Respond Well To Treatment

ScienceDaily describes research indicating that Positron Emission Tomography (PET) is more accurate than conventional imaging in identifying patients who have good responses to chemotherapy and radiation treatment.

Link: ScienceDaily: Imaging Technology Helps Identify Esophageal Cancer Patients Who Respond Well To Treatment

New research at Wake Forest University Baptist Medical Center shows that Positron Emission Tomography (PET) is more accurate than conventional imaging in identifying patients who have good responses to chemotherapy and radiation treatment -- a finding that could one day help some patients avoid surgery.

The results, from a study of 64 patients with esophageal cancer, are published in the April issue of Annals of Surgery. PET, a technology that produces images of the metabolic function of tissue, was used to test patients for cancer after treatment with a combination of chemotherapy and radiation (chemoradiation).

Over the past two decades, the most common treatment for esophageal cancer has been chemoradiation followed by surgery. Even with these treatments, the prognosis is poor for most patients, with long-term control rates of 25 to 35 percent. Some patients, however, respond well to chemoradiation and have improved long-term survival.

Identifying which patients will respond to chemoradiation alone -- and perhaps avoid surgery to remove part of the esophagus -- has been difficult. Conventional imaging, including both computed tomography (CT) and endoscopic ultrasound (EUS), are poor predictors of response to chemoradiation.

Recently, PET was shown to be more accurate than CT and EUS in evaluating newly diagnosed patients to determine the extent of the disease. So, Wake Forest researchers decided to evaluate its ability to determine response to chemoradiation.

This study was supported, in part, by a grant from the National Cancer Institute.

Esophageal Cancer and Acid Reflux

Yahoo News describes the increased risk for cancer from chronic heartburn and treatment options for esophageal cancer.

Link: Docs Debate Esophageal Cancer Treatment - Yahoo! News

Chronic heartburn appears to be fueling the nation's fastest-growing cancer, esophageal cancer. Some 3 million Americans are thought to have a type of esophagus damage from severe acid reflux that puts them at increased risk for the deadly cancer — and new research is exploring whether it's possible to zap away that damage and block the cancer from ever forming.

"The million-dollar question is can we prevent cancer," says Dr. V.K. Sharma of the Mayo Clinic in Scottsdale, Ariz., who is leading one of the newest studies, using radiofrequency energy to burn away the damage. "That has not been answered."

But it's a question taking on new urgency as doctors chart a six-fold increase in the last two decades in the main type of esophageal cancer.

About 14,550 Americans will be diagnosed with esophageal cancer this year, the American Cancer Society estimates. Most won't be diagnosed until they feel such symptoms as trouble swallowing and loss of appetite. The prognosis is grim: Just 16 percent of esophageal cancer patients survive five years, and 13,770 are predicted to die this year.

Most have esophageal adenocarcinoma, the type linked to severe chronic heartburn.

The only treatment completely proven to prevent esophageal cancer is to cut out that part of the esophagus, a high-risk operation, conclude Spechler and colleague Dr. Rhonda Souza, who recently reviewed the evidence in an American Cancer Society journal.

The less invasive Barrett's treatments haven't been studied long enough to know if they'll really eliminate the cancer risk, or if it will just return — and they, too, cause some side effects, the pair caution.

Still, the treatments do offer an option for patients too old or ill for major esophagus surgery, says Dr. Prateek Sharma of the University of Kansas School of Medicine, a spokesman for the American Gastroenterological Association. And for those with those precancerous dysplasia spots, they're a potential middle ground.

One thing all agree on: Every Barrett's patient needs high-powered medication to control their acid reflux, even those who don't complain of heartburn symptoms. The esophagus may simply be too scarred to feel the pain anymore.

Promising research is under way that suggests a genetic marker may soon be able to tell which Barrett's patients are at highest risk for cancer, and which can relax, Souza adds.

Genetic Tests Can Miss Breast Cancer-Causing Mutations

The American Cancer Society reports on research that women with a specific genetic mutation have more than five times the lifetime risk of breast cancer.

Link: ACS :: Genetic Tests Can Miss Breast Cancer-Causing Mutations

Genetic testing for mutations that can cause breast cancer isn't as accurate as it needs to be, new research in the Journal of the American Medical Association suggests. Up to 12% of people who test negative for mutations to BRCA1 and BRCA2 may, in fact, have a dangerous change in those genes, researchers from the University of Washington said today.

People in this situation don't have all the information they need to make the best decisions about how to protect themselves from developing cancer, said study coauthor Mary-Claire King, PhD, an American Cancer Society Research Professor in the departments of medicine and genomic sciences at the University of Washington.

A woman with no BRCA mutations has about a 13% lifetime risk of breast cancer, while a woman with a mutation has an 80% lifetime risk.

Between 5% and 10% of breast cancers in white women in the US are thought to be caused by inherited changes in the BRCA1 and BRCA2 genes. These mutations are also responsible for 10% to 15% of ovarian cancers in white women in this country. These mutated genes can be passed on from both fathers and mothers. Women who come from families where many members have had breast or ovarian cancer are often advised to get tested to see if they carry one of the BRCA mutations that puts them at very high risk of developing one of these diseases.

Women who test positive may decide to get more frequent mammography screening for breast cancer, or may decide to get screened with other tests like magnetic resonance imaging, in addition to mammography. They may be able to take tamoxifen, a drug shown to reduce the risk of breast cancer in high-risk women.

Citation: "Spectrum of Mutations in BRCA1, BRCA2, CHEK2, and TP53 in Families at High Risk of Breast Cancer." Published in the March 22/29, 2006 Journal of the American Medical Association (Vol. 295, No. 12: 1379-1388). First author: Tom Walsh, PhD, Departments of Medicine and Genomic Sciences, University of Washington, Seattle.

Less Invasive Surgery Shows Promise for Kidney Cancer

The American Cancer Society reports that a less invasive type of surgery for kidney cancer offers good short term results.

Link: ACS :: Less Invasive Surgery Shows Promise for Kidney Cancer

Summary: A less invasive type of surgery for kidney cancer offers good results, at least in the short term, researchers report in the Journal of Urology. A team from the Cleveland Clinic Foundation says patients fared well when their tumors were removed laparoscopically -- using a few small incisions instead of opening the entire abdomen. But the procedure is complicated and requires expert surgeons, they warn.

Why it's important: Surgery is the primary treatment for kidney cancer, which is expected to strike nearly 39,000 people in the US in 2006. Many patients have their entire kidney removed, but some require or are eligible for partial nephrectomy, surgery that only removes the diseased part of the kidney and leaves the rest intact. This procedure is usually done by opening the abdomen. In recent years doctors have begun experimenting with laparoscopic surgery (also called keyhole surgery) because patients typically recover faster and experience less pain than with traditional open surgery.

The bottom line: The researchers call their findings "encouraging" because they appear similar to results with traditional open surgery. About 10%-20% of people who get open partial nephrectomy die of their cancer within 5 years of the operation, the authors say. But they caution that their follow-up isn't long enough to know for certain that keyhole surgery is just as safe and effective as traditional partial nephrectomy. It's also not clear that the results would be as good if patients were treated by less experienced physicians.

Citation: "Laparoscopic Partial Nephrectomy: 3-Year Followup." Published in the February, 2006, Journal of Urology (Vol. 175, No. 2: 459-462). First author: Alireza Moinzadeh, MD, State University of New York Upstate Medical University (formerly at Cleveland Clinic Foundation).

Search-and-destroy molecule targets cancer

Science Blog describes research at the University of Illinois at Chicago on a compound called ARC causes tumor cells to die but leaves normal cells unharmed. Excerpts below.

Link: Search-and-destroy molecule targets cancer

A man-made chemical compound called ARC causes tumor cells to die but leaves normal cells unharmed, researchers at the University of Illinois at Chicago report in a study highlighted in the March 15 issue of Cancer Research. ARC also proved to have strong anti-angiogenic properties, showing promise as an inhibitor of new blood vessel formation in tumors.

ARC, an acronym for its long chemical name, resembles one of the bases that are the building blocks of DNA. Researchers found it by screening more than 2,000 compounds for their ability to inhibit a key step in the cell cycle. Previous studies had shown that blocking that step spurs apoptosis, or cell suicide, in cancer cells.

When cancer cells (human lung cells that had been transformed by a virus to become cancerous) were treated with ARC, 50 to 70 percent killed themselves within 24 hours. Normal lung cells exposed to two to four times higher concentrations of ARC were unharmed.

Our results suggest that while ARC induces cell death in tumor cells very efficiently, it only causes a cell-cycle block in normal cells," said Andrei Gartel, assistant professor of molecular genetics at UIC and principal investigator on the study. "This gives ARC an important advantage as a potential anticancer drug, because many of the drugs currently used to fight cancer are also toxic to normal cells."

In other experiments, Gartel said, ARC induced cell suicide in breast, colon, gastric and liver cancer cell lines.

An important aspect of ARC-induced cell suicide, Gartel said, is that it does not rely on p53, a normal protein in cells that is often responsible for initiating cell death after the cell has been treated with cancer drugs. The problem, he said, is that in more than half of all human tumors p53 has been inactivated.

Gartel said while it is not yet known how ARC induces apoptosis in cancer cells, his group has shown that in normal cells the molecule inhibits RNA synthesis, a key step in gene expression.

The study was funded by the UIC Department of Medicine, the Illinois Department of Public Health and the National Institutes of Health.

From University of Illinois at Chicago [1]