Potential new target for cancer found

By bypassing a well-known gene implicated in almost one-third of all cancers and instead focusing on the protein activated by the gene, Duke University Medical Center researchers believe they may have found a new target for anti-cancer drugs.

In experiments with human cells and animal models, the researchers studied the gene known as “Ras,” which is integral in normal cell growth. When this gene is mutated and becomes overactive, it can lead to the unregulated proliferation of cells that is the hallmark of tumor formation.

The ras gene, known as an oncogene when it is in this mutated state, has been implicated in several different cancers, including those of the pancreas and lungs. To date, efforts at blocking or turning off ras have proven ineffective. Pancreatic cancer has been shown to have the strongest link to the ras oncogene, and it is also one of the hardest cancers to treat, with few patients alive five years after diagnosis, researchers said.

“Since it has been so difficult to target the ras gene itself with drugs, we tried to determine if something that ras activates could be a possible target for a drug or therapy,” said Christopher Counter, Ph.D., associate professor of pharmacology and cancer biology and senior member of the research team. “We found a specific target that could be susceptible to drugs, and if these findings are proven true in human trials, we could have a new way of treating ras-dependent cancers.”

The results of the Duke experiments were published July 15, 2007, in the journal Genes & Development. Brooke Ancrile, a graduate student in Counter’s laboratory, was first author of the paper. The research was supported by the National Institutes of Health.

The researchers discovered that the overactive ras gene was responsible for above-normal secretion of a factor known as interleukin-6 (IL-6). Scientists know a great deal about IL-6 and its functions in the body, but its link to oncogenic ras was unknown.

In addition to finding that the ras oncogene spurred the production of IL-6, they also found that inhibiting IL-6 production reduced the creation of new blood vessels, which are crucial for the development and nourishment of tumors.

“IL-6 was like the gas pedal driving the growth of tumors,” Counter said. “No gas, no growth, which is exactly what we saw when we inhibited IL-6 in tumors.”

Counter is encouraged that even though these findings are in cell culture and animal models, therapies based on targeting IL-6 in cancers driven by the ras oncogene could be tested in humans in the near future. A biotechnology company has already developed a monoclonal antibody specific to IL-6 which could be used to neutralize IL-6.

A phase II trial is underway testing a monoclonal antibody against IL-6 for patients with multiple myeloma, a cancer that depends on IL-6 but is not known to have a connection to the ras oncogene. If the results of this trial are positive, studies might begin in ras-dependent cancers. Counter’s group is actively pursuing the idea that such an antibody may inhibit pancreatic cancer growth in mouse models. If these results are positive, this will open the door for Duke oncologists to organize a clinical trial to test the agent in human cancer patients.

“Secreted proteins promoting the growth of blood vessels in tumors have been successfully neutralized in the past with antibodies,” Ancrile said. “We believe that IL-6 is a viable target for drugs that holds promise in the treatment of cancers dependent on the ras oncogene.”

Source: Duke University Medical Center

Related stories:

Cellular senescence a double-edged sword
Scientists have identified a molecular cause behind the ravages of old age and in doing so have also shown how a natural process for fighting cancer in younger persons can actually promote cancer in older individuals. Cellular senescence, the process by which biological cells stop dividing in response to stress or damage to their DNA, was shown to trigger the secretion of proteins that cause inflammation in neighboring cells and tissue. Inflammation is linked to almost every major disease associated with aging, including many cancers.
Combining targeted therapy drugs may treat previously resistant tumors
A team of cancer researchers from several Boston academic medical centers has discovered a potential treatment for a group of tumors that have resisted previous targeted therapy approaches.
Iressa proves just as effective as chemotherapy for lung cancer
Gefitinib, also known as Iressa, the once-promising targeted therapy for the treatment of non-small cell lung cancer, has proven as effective as chemotherapy as a second-line therapy for the disease with far fewer side effects, according to an international Phase III clinical trial, led by researchers at The University of Texas M. D. Anderson Cancer Center.
Misreading of damaged DNA may spur tumor formation
The DNA in our cells is constantly under assault from oxygen, the sun's radiation and environmental stresses. Most of the time, our cells can repair the damage before it gets copied into a permanent mutation that could lead to cancer.
Study of learning disabled mice shows balance in the brain is key
A new study in the October 31st issue of Cell, a Cell Press journal, has revealed the molecular and cellular underpinnings of one of the most common, single gene causes for learning disability in humans. The findings made in learning disabled mice offer new insight into what happens in the brain when we learn and remember.
New results help predict treatment response in colorectal cancer
Genetic testing can identify a group of patients with advanced colorectal cancer who are likely to survive on average twice as long if treated with the drug cetuximab, late breaking results show.
Rheb's role in cancer
Two independent papers in the August 15th issue of G&D identify the Rheb GTPase as a novel oncogene and a promising new chemotherapeutic target.
Gene's newly explained effect on height may change tumor disorder treatment
A mutation that causes a childhood tumor syndrome also impairs growth hormone secretion, researchers at Washington University School of Medicine in St. Louis have found.

News discussion:

Medicine & Health news