The observation that people taking medication for schizophrenia have lower cancer rates than other people has prompted new research revealing that anti-psychotic drugs could help treat some major cancers.

A preliminary finding in the current online issue of the International Journal of Cancer reports that the anti-psychotic drug, pimozide, kills lung, breast and brain cancer cells in in-vitro laboratory experiments.

Several epidemiological studies have noted the low rate of cancer among schizophrenic patients. These studies found, for example, that these patients have lower rates of lung cancer than other people, even though they are more likely to smoke.

Genetic factors and the possibility of reduced cancer detection in patients have been considered and over the past decade anti-psychotic drugs have been suggested as possible mediators of this effect.

In the new study, pimozide was the most lethal of six anti-psychotic drugs tested by a team from UNSW and the University of Queensland. Rapidly-dividing cancer cells require cholesterol and lipids to grow and the researchers suspect that pimozide kills cancer cells by blocking the synthesis or movement of cholesterol and lipid in cancer cells.

Analysis of gene expression in test cancer cells showed that genes involved in the synthesis and uptake of cholesterol and lipids were boosted when pimozide was introduced.

To test the idea that pimozide acts by disrupting cholesterol homeostasis, the researchers combined pimozide with mevastatin, a drug that inhibits cholesterol production in cells. The two drugs were more lethal in combination against cancer cells than when either drug was used alone.

“The combination of pimozide and mevastatin increased cancer cell death,” says UNSW researcher Dr Louise Lutze-Mann, a co-author of the study. “We needed a lower dose of each drug to kill the same amount of cells.”

Although side-effects are associated with the use of high doses of these drugs - such as tremors, muscle spasms and slurred speech - these effects are considered to be tolerable in patients where other treatments have failed and the drugs will only be used short-term. These side-effects would be reduced if the drugs were used in combination with a lipid-lowering drug, such as mevastatin.

The researchers have also investigated the effects of olazapine , a “second-generation” antipsychotic drug, and found that it also kills cancer cells but has a better side-effect profile. When administered to patients, it accumulates in the lung, which suggests that it may prove to be most useful in treating lung cancer.

The researchers are now testing these drugs on tumour cells from brain cancers since these tumours are extremely difficult to treat and are frequently associated with poor patient prognosis. Patients diagnosed with glioblastoma, for example, survive less than one year.

The results are very promising as these drugs are greater than 50-fold more effective at killing glioblastoma cells than the chemotherapeutic drug currently in use. The researchers are also investigating the effects of these drugs on cells derived from drug-resistant childhood cancers where current chemotherapy has failed.

Another hopeful prospect is an investigation of another group of drugs, called SERMs, which are similar in structure to the antipsychotic drugs but have far fewer side-effects associated with them.

Source:
Dr. Louise Lutze-Mann

University of New South Wales

Dentists in Somerset are advising patients that regular dental checks remain the best way for the early detection of serious health problems, such as mouth cancer.

The recommendation comes on the heels of a new report from Cancer Research UK which claims that alcohol is largely to blame for a worrying rise in the rate of oral cancers among men and women in their 40s. In the UK numbers of cancers of the lip, mouth, tongue and throat in this age group have risen by 26% in the past decade.

Commenting upon the charity’s findings, Martin Fulford, NHS Somerset’s Dental Advisor, said: “Mouth cancer can be treated successfully if diagnosed early. Tobacco remains the main risk factor for oral cancer but for people in their 40s, there are also other factors contributing to this jump in oral cancer rates.

“This latest report suggests alcohol consumption has doubled since the 1950s and this might be contributing to the upward trend in mouth cancers we are seeing throughout the UK.
People in Somerset have good access to NHS dental care. However, early detection of mouth cancer is essential if see are to see a reduction in the 1,800 deaths across the UK which occur each year. “

Source
NHS Somerset

Emory University’s Chemical Biology Discovery Center has been selected by SAIC-Frederick, Inc. (SAIC-F) to be part of an 11-member national consortium aimed at accelerating the discovery and development of new and innovative, targeted cancer therapies. SAIC-F is the prime contractor to the National Cancer Institute at Frederick (NCI-Frederick).

The national Chemical Biology Consortium (CBC) will bridge the gap between basic scientific investigation and clinical research supported by the NCI. The consortium will focus on unmet medical needs, such as drugs that are of low interest to the pharmaceutical industry but that could have significant benefit for patients. It is expected to bring the skills of hundreds of chemical biologists, oncologists, and synthetic and medicinal chemists to bear on particularly challenging problems in molecular oncology.

Examples of the CBC’s innovative discovery pathways could include re-engineering investigators’ assays into high-throughput screens; rapidly synthesizing natural products that show promise as drug targets in a particular form of cancer; making new compounds water-soluble; and accelerating the development of drug candidates with great clinical promise.

As one of three Specialized Application Centers in the NCI Consortium, the Emory Chemical Biology Discovery Center will focus its broad capability and special expertise on protein-protein interactions in cancer through assay development and implementation, high-throughput screening, medicinal chemistry optimization and informatics, with the participation of an intellectual property specialist.

“Recent advances in our understanding of the molecular basis of cancer have led scientists to identify oncogenes and pathways involved in tumor development that offer unprecedented opportunities for innovative drug discovery,” says Haian Fu, PhD, director of the Emory Chemical Biology Discovery Center and principal investigator of the Emory CBC center. Fu is professor of pharmacology, hematology & medical oncology in Emory University School of Medicine and a co-leader of the Discovery and Developmental Therapeutics Program of the Emory Winship Cancer Institute.

“This consortium will allow the NCI and the consortium members to pursue innovative strategies and dedicate resources to interrogating new signaling pathways and promising but difficult targets for the rapid discovery and development of clinically viable new compounds that might not otherwise be developed. Examples include pediatric cancer targets,” says Fu.

The Emory center is anchored by investigators within the Emory Winship Cancer Institute and integrated with drug discovery and development capabilities of researchers throughout campus. Co-principal investigators of the Emory CBC Center are Fadlo Khuri, MD, deputy director for clinical and translational research in Emory Winship Cancer Institute and professor and chair of hematology & medical oncology, and Dennis Liotta, PhD, Emory professor of chemistry.

“Emory has a strong foundation of team science and collaboration, high throughput screening expertise and a solid record of success in the NIH Molecular Libraries Screening Centers Network,” says Liotta. “We have a team of assay biologists, screening scientists and informatics experts working side by side with medicinal chemists. Our record of drug discovery and partnerships with pharmaceutical companies show that we have the experience and expertise to serve as national leaders in cancer drug discovery.”

The Georgia Cancer Coalition (GCC) is providing matching funds for the Emory CBC Center of approximately $750,000. Emory will provide other matching funds for the Center. The Georgia Research Alliance provided initial support for the Chemical Biology Discovery Center.

“We are proud and delighted that the National Cancer Institute has once again reached out to Georgia for leadership in cancer control,” says William J. Todd, president and chief executive officer of the Georgia Cancer Coalition. “By supporting Emory’s participation in this national cancer drug discovery initiative, we are reinforcing the state’s comprehensive cancer control plan goal to accelerate improvements in cancer treatment. This designation brings us yet one step closer to making Georgia one of the nation’s premier states for cancer control.”

“As a molecular oncologist and a cancer clinician, I am very pleased with this opportunity for Emory’s involvement in a national NCI consortium to speed drug discovery,” says Khuri. “This is a very exciting time for cancer research, and I am optimistic this consortium will result in significant research advances that soon will benefit patients with particularly challenging types of cancer.”

As a member of the national consortium, the Emory center will join forces with the NCI and other national centers for project-team based accelerated cancer drug discovery operations from target identification, high throughput screening, all the way through clinical trials. It will be funded through a contractual agreement mechanism with the NCI.

In 2005 the National Institutes of Health (NIH) awarded Emory $9 million in the pilot phase of the National Molecular Libraries Screening Center Network (MLSCN). The network uses high-tech screening methods on huge libraries of small molecular compounds to identify probes as promising molecular research tools.

Emory’s CBC selection by the NCI built on Emory’s already established Chemical Biology Discovery Center and its experience in MLSCN. The Emory Chemical Biology Discovery Center is an interdisciplinary collaboration among research departments in Emory School of Medicine and Emory College. The Center also uses high-throughput technologies to screen libraries of hundreds of thousands of small molecule compounds against promising molecular targets identified by Emory scientists.

Source:
Holly Korschun

Emory University