FDA on Friday approved expanding the use of Merck’s human papillomavirus vaccine Gardasil to protect against cancers of the vagina and vulva, the AP/MSNBC.com reports (AP/MSNBC.com, 9/12). According to an FDA release, Gardasil first was approved by FDA in 2007 for girls and women ages nine to 26 to prevent cervical cancer cases caused by HPV strains 16 and 18, genital warts cases caused by HPV strains 6 and 11, and precancerous genital lesions caused by HPV strains 6, 11, 16 and 18. FDA in June denied Merck’s request to approve the vaccine for women ages 27 to 45.

Jesse Goodman, director of FDA’s Center for Biologics Evaluation and Research, said that there now is “strong evidence” that Gardasil “can help prevent vulvar and vaginal cancers due to the same viruses for which it also helps protect against cervical cancer.” Although vaginal and vulvar cancers are “rare,” the “opportunity to help prevent them is potentially an important additional benefit from immunization against HPV,” Goodman said (FDA release, 9/12).

According to the AP/MSNBC.com, Merck followed about 15,000 women over a two-year period as part of a clinical study for the vaccine. One group of participants was given the vaccine and the other was not. Ten women in the group that did not receive the vaccine developed precancerous vulvar lesions and nine developed similar vaginal lesions because of HPV infection. No women in the Gardasil group developed such lesions (AP/MSNBC.com, 9/12).

Rick Haupt, head of Merck’s clinical research program for Gardasil, said that the clinical trials found the vaccine to be 100% effective in preventing the two cancers and that additional follow-up to the trials has given researchers “more rigorous data” (Reuters, 9/12). Haupt also said that the availability of Gardasil as prevention for the two additional cancers is “fabulous stuff,” adding that Merck is studying the effectiveness of the vaccine in men with the aim of submitting data to FDA by the end of the year (Favole, Dow Jones/Morning Star, 9/12).

FDA noted that Gardasil does not protect against HPV infections that women might already have at the time of vaccination and encouraged women to get regular Pap tests even after they have been vaccinated (FDA release, 9/12).

Reprinted with kind permission from http://www.nationalpartnership.org. You can view the entire Daily Women’s Health Policy Report, search the archives, or sign up for email delivery here. The Daily Women’s Health Policy Report is a free service of the National Partnership for Women & Families, published by The Advisory Board Company.

© 2008 The Advisory Board Company. All rights reserved.

View drug information on Gardasil.

Doctors in Switzerland have carried out the country’s first clinical treatments using RapidArc™ technology from Varian Medical Systems. Professor Franco Cavalli, president of the UICC (International Union Against Cancer), symbolically pushed the ‘beam-on’ button to mark the occasion as the first of two anal canal cancer patients became the first person in the country to benefit from this advanced form of intensity-modulated radiotherapy (IMRT).

Dr. Antonella Fogliata, head of medical physics at the Istituto Oncologico della Svizzera Italiana (IOSI) in Bellinzona, said, “Both treatments were very fast and smooth and took about seventy seconds to deliver. Previous comparable IMRT treatments would have taken about twenty minutes so there are some real benefits to using RapidArc, especially with regards to the comfort of the patient. We think it will make a real difference to cancer patients, particularly those with tumors in the pelvic region.”

Clinicians delivered the final boost of each patient’s scheduled radiotherapy course using RapidArc. They are believed to be the first anal canal cancer patients in the world to be treated using the fast and efficient new technology, which was introduced by Varian earlier this year.

Professor Cavalli, medical director of the hospital and a globally known medical oncologist, said, “It was a tremendous pleasure to be involved and I want to congratulate the team on a fantastic job.”

IOSI, a comprehensive cancer center in the region of Ticino, treats cancer patients using two linear accelerators. The hospital has a history of pioneering advanced radiotherapy techniques, having been the first in Switzerland to treat using IMRT in 2001. Now IOSI has become the first non-university hospital in Europe to implement clinical Varian RapidArc treatments. Luca Cozzi, PD, research co-ordinator at IOSI and co-ordinator of Varian’s RapidArc Council of pioneering hospitals, was instrumental in this landmark being achieved.

Clinician Dr. Alessandra Franzetti Pellanda said, “The first patients fully realised the relevance of this innovation and were proud to be asked to start this new era of radiation oncology at IOSI. They see the RapidArc project as a clear message of commitment of the clinic towards their daily needs and their future.”

“The quality of these treatments gives us confidence that most of the pelvic area will benefit from the use of RapidArc,” she added. “We will also investigate other sites like breast with concomitant integrated boost, esophagus and the known sites like head and neck and base of the skull where colleagues from other centers are already active.”

RapidArc delivers a volumetric intensity-modulated radiation therapy treatment in a single or multiple arcs of the treatment machine around the patient and makes it possible to deliver advanced image-guided IMRT two to eight times faster than is possible with conventional IMRT. Treatment planning analyses show that Varian’s RapidArc matches or exceeds the precision of conventional IMRT systems and spares more of the healthy tissue surrounding the tumor. Unrelated clinical studies on radiotherapy correlate the ability to spare more healthy tissue with reduced complications and better outcomes.

“RapidArc extends the versatility of Varian’s image-guided radiotherapy system, adding volumetric arc therapy to other advanced capabilities including fixed-beam IMRT and stereotactic treatments,” says Rolf Staehelin, Varian’s European marketing director. “By outfitting their treatment machine with this new capability, clinicians such as those at IOSI will be able to offer cancer patients an optimized treatment according to each patient’s specific needs.”

About Varian Medical Systems

Varian Medical Systems, Inc., of Palo Alto, California, is the world’s leading manufacturer of medical devices and software for treating cancer and other medical conditions with radiotherapy, radiosurgery, proton therapy, and brachytherapy. The company supplies informatics software for managing comprehensive cancer clinics, radiotherapy centers and medical oncology practices. Varian is a premier supplier of tubes and digital detectors for X-ray imaging in medical, scientific, and industrial applications and also supplies X-ray imaging products for cargo screening and industrial inspection. Varian Medical Systems employs approximately 4,800 people who are located at manufacturing sites in North America and Europe and in its 60 sales and support offices around the world.

Varian Medical Systems

In battles against chronic infections, the body’s key immune cells often become exhausted and ineffective. Researchers at The Wistar Institute have found a way to restore vigor to these killer T cells by blocking a key receptor on their surface, findings that may advance the development of new therapies for diseases such as HIV, hepatitis B and C, and cancer.

In their study, published online September 15 in the Proceedings of the National Academy of Sciences (PNAS), Wistar Institute investigators and colleagues report that using an antibody to block the receptor, known as programmed death-1 (PD-1), dramatically restored immunity in chronically infected mice. Furthermore, they discovered a method to distinguish between T cells that can be revitalized in this way and those that can’t.

The findings will help researchers develop PD-1 blocking agents, and also provide a way to select patients who may benefit most from such novel drugs, says the study’s lead author E. John Wherry, Ph.D., an assistant professor in Wistar’s Immunology Program.

“Blocking PD-1 may provide a novel tool to fight chronic infection as well as some cancers, like melanoma, that are susceptible to destruction by the immune system,” Wherry said. Examples of infections that often result in T-cell exhaustion are HIV, hepatitis B, and hepatitis C, he says.

Wherry’s continuing research on PD-1 has provided the groundwork for developing antibody therapies that inhibit the receptor. Wherry says he knows of a pharmaceutical company preparing to test one of these agents in patients with hepatitis C.

Researchers have known that T cells - white blood cells capable of inducing the death of infected or cancerous cells - become progressively less functional over time. In earlier studies, Wherry and his colleagues found that, during the course of a chronic infection, gene expression in killer T cells changed dramatically as the cells became exhausted and immune response to a pathogen slowed down. Wistar investigators then identified one gene that played a central role in this tamping down of immune response - PD-1, which produces PD-1 protein receptors that stud the surface of these T cells.

In follow-up experiments, they found that if they blocked PD-1 receptors in cell cultures using an antibody made up of one of the protein’s natural binding ligands they could alleviate T-cell exhaustion. This demonstrated that PD-1 serves as a “brake” on T-cell function.

Wherry suspects that this reaction is designed to protect a body against the ravages that a chronically over-stimulated immune system can wreak. “The immune system can cause a lot of damage in an effort to control an infection. If you can’t clear an infection and are making yourself sick trying to do so, it may be better off to live with the infection than die from the immune-mediated collateral damage,” he said.

In the current study, Wherry and colleagues tested in mice infected with lymphocytic choriomeningitis virus the effect of plugging the PD-1 receptor with the antibody, thus releasing the “brake” on the immune system. And they studied two different subsets of killer T cells: those with the highest expression of PD-1 receptors and ones with an “intermediate” expression. Researchers theorized that those T cells with the highest PD-1 expression, signifying the deepest exhaustion, would benefit most from an antibody to PD-1.

To their surprise, that is not what they found. They implanted these two different subsets of cells into infected mice, and then gave the mice a PD-1 antibody. Those mice implanted with T cells with intermediate expression of PD-1 recovered their vigor, while mice with the highest PD-1 expression did not. “It may be the killer T cells expressing a lot more PD-1 are already committed to cell death,” Wherry said.

Knowing which subset of T cells will respond to an antibody drug will help physicians identify patients who could respond, if these novel agents reach extensive clinical testing, Wherry says. “We can optimize the promise of such a medical tool and minimize wasteful treatment,” he said.

Wherry says this study provides insights into how potential PD-1 agents can be refined so as not to provoke an autoimmune response, in which the body errantly attacks its own tissue. And in the same way, it suggests strategies by which to disarm autoimmune disorders, such as lupus, he says. “If we can understand how to turn PD-1 off to enhance immunity, this will provide insights on how to turn it on to treat autoimmune disorders,” Wherry said.

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Wistar’s Shawn D. Blackburn and Haina Shin assisted with the study, along with Gordon J. Freeman, Ph.D., of the Dana-Farber Cancer Center.

The research was supported by grants from the National Institutes of Health and the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries - Tomorrow’s Cures. On the Web at http://www.wistar.org/.

Source: Staci Vernick Goldberg
The Wistar Institute

A comprehensive document listing and comparing 17 mainstream treatment options for prostate cancer has been published by the Dattoli Cancer Center & Brachytherapy Research Institute in Sarasota.

“Prostate Cancer Treatment Options - The Facts” was premiered September 6 at the Prostate Cancer Research Institute’s annual international conference in Los Angeles.

The alphabetical listing runs from Cryotherapy to Watchful Waiting, and includes a brief description, pros, cons and information on published success rates of the most common treatment options available throughout the US. “This is the tool that newly diagnosed men have been searching for,” says Michael Dattoli, MD, founder and physician in chief of the world-renowned Dattoli Cancer Center.

Over 200,000 men are diagnosed with this disease annually, actually more than the number of women diagnosed annually with breast cancer. In the past 5 years there has been an explosion in new treatment options - including robotics for surgery and novel radiation applications.

“The challenge remains how to kill the cancer cells without permanently damaging the critical structures which surround the walnut-sized gland,” Dattoli adds. Depending on the stage of the disease when diagnosed and the experience level of the treating physician, treatment has too often left the man impotent and/or incontinent. Newer therapies are designed to protect these functions while destroying the malignant prostate cancer cells, but many have not yet proven their effectiveness.

Copies of “The Facts” document are available by contacting the Dattoli Cancer Center, or downloading it from the website: http://www.dattoli.com

Dattoli Cancer Center

This week, University of Michigan scientists will begin a phase 1 clinical trial for the treatment of cancer-related pain, using a novel gene transfer vector injected into the skin to deliver a pain-relieving gene to the nervous system.

A gene transfer vector is an agent used to carry genes into cells. In this groundbreaking clinical trial, the investigators will use a vector created from herpes simplex virus (HSV) - the virus that causes cold sores - to deliver the gene for enkephalin, one of the body’s own natural pain relievers.

“In pre-clinical studies, we have found that HSV-mediated transfer of enkephalin can reduce chronic pain,” says David Fink, M.D., Robert Brear Professor and chair of the department of neurology at the U-M Medical School. Fink developed the vector with collaborators and will direct the study.

“After almost two decades of development and more than eight years of studies in animal models of pain, we have reached the point where we are ready to find out whether this approach will be effective in treating patients,” Fink says. The investigators are recruiting 12 patients with intractable pain from cancer to examine whether the vector can be used safely to deliver its cargo to sensory nerves.

The trial represents two firsts, says Fink: It is the first human trial of gene therapy for pain, and the first study to test a nonreplicating HSV-based vector to deliver a therapeutic gene to humans. Fink says the technique may hold promise for treating other types of chronic pain, including pain from nerve damage that occurs in many people with diabetes.

The HSV vector, genetically altered so it cannot reproduce, has a distinct advantage, Fink says: “Because HSV naturally travels to nerve cells from the skin, the HSV-based vector can be injected in the skin to target pain pathways in the nervous system.”

Gene therapy for pain

Chronic pain is an important clinical problem that, despite a wide array of therapeutic options, cannot be effectively treated in a substantial number of patients. Fink notes that one key problem in treating pain is that the targets of conventional pain-relieving medications tend to be widely distributed in the nervous system, so that “off target” side effects of the drugs often preclude the use of those drugs at fully effective doses.

“This provides the rationale for using gene transfer to treat pain,” Fink says. “We use the vector to deliver and express a chemical that breaks down very quickly in the body. The targeted delivery allows us to selectively interrupt the transmission of pain-related signals and thus reduce the perception of pain.”

Enkephalin is one member of the family of opioid peptides that are naturally produced in the body. Opioid peptides exert their pain-relieving effects by acting at the same receptor through which morphine and related opiate drugs achieve their pain-relieving effects. In this trial the enkephalin peptide, produced as a result of the gene transfer, will be released selectively in the spinal cord at a site involved in transmitting pain from the affected body part to the brain.

“We hope that this selective targeting will result in pain-relieving effects that cannot be achieved by systemic administration of opiate drugs, ” Fink says. “This trial is the first step in bringing the therapy into clinical use. A treatment is at least several years off.”

Preclinical studies led to human trial

The phase I clinical trial represents the culmination of studies performed by investigators working in the U-M laboratory co-directed by Fink and his wife, Marina Mata, M.D., also a professor of neurology at U-M, along with colleagues at the University of Pittsburgh led by Joseph Glorioso, Ph.D. In published studies, the researchers have demonstrated that HSV-mediated gene transfer is effective in rats with pain resulting from inflammation, nerve damage or spinal cord injury, and in mice with pain caused by cancer. The extensive preclinical data in animal models were reviewed by the Recombinant DNA Advisory Committee at the National Institutes of Health. The Food and Drug Administration approved an investigational new drug application for the therapy in February.

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Funding for the preclinical studies was provided by the NIH, and related studies of the vector were funded by grants from the Department of Veterans Affairs and the Juvenile Diabetes Research Foundation. The human trial is supported by a research grant from Diamyd, Inc., a subsidiary of Diamyd Medical (DIAMB.ST), a publicly traded Swedish biotechnology company. Fink has no financial interest in or consulting relationship with Diamyd. He is an inventor on patents related to this work that are owned by the University of Pittsburgh and licensed to Diamyd. Susan Urba, M.D. and Frank Worden, M.D., medical oncologists at the U-M Comprehensive Cancer Center will serve as principal clinicians for the study, assisted by Suzette Walker, N.P., who will serve as study coordinator, and Heidi L’Esperance, who will serve as data manager.

Trial details

The investigators are seeking patients with intractable pain related to cancer that is unresponsive to maximally tolerated doses of conventional analgesic drugs. The vector will be delivered in 10 small injections into the skin, and will require an overnight stay in the Michigan Clinical Research Unit at U-M Hospital. For more information visit:

http://www.umengage.org/

http://www.cancer.med.umich.edu/research/clinical_trials.shtml

http://www.med.umich.edu/neurology

Source: Anne Rueter
University of Michigan Health System

Nanoparticles filled with a drug that targets two genes that trigger melanoma could offer a potential cure for this deadly disease, according to cancer researchers. The treatment, administered through an ultrasound device, demonstrates a safer and more effective way of targeting cancer-causing genes in cancer cells without harming normal tissue.

“It is a very selective and targeted approach,” said Gavin Robertson, associate professor of pharmacology, pathology and dermatology, Penn State College of Medicine. “And unlike most other cancer drugs that inadvertently affect a bunch of proteins, we are able to knock out single genes.”

The Penn State researchers speculated that “silencing RNA” (siRNA) — strands of RNA molecules that knock out specific genes — could turn off the two cancer-causing genes and potentially treat the deadly disease more effectively.

“siRNA checks the expression of the two genes, which then lowers the abnormal levels of the cancer causing proteins in cells,” explained Robertson, who is lead author of the paper appearing in the Sept. 15 issue of the journal Cancer Research.

In recent years, researchers have zeroed in on two key genes — B-Raf and Akt3 — that cause melanoma. B-Raf, the most frequently mutated gene in melanoma, produces the mutant protein, B-Raf, which helps mole cells survive and grow but does not form melanomas on its own.

Robertson and colleagues previously found that a protein called Akt3 regulates the activity of the mutated B-Raf, which aids the development of melanoma.

The drug in this study specifically targets Akt3 and the mutant B-Raf and does therefore not affect normal cells, added Robertson, who is also director of the Foreman Foundation Melanoma Therapeutics Program at the Penn State College of Medicine Cancer Institute.

However, while knocking out specific genes may seem like a straightforward task, delivering the siRNA drug to cancerous cells is another story, because protective layers in the skin not only keep drugs out, but chemicals in the skin quickly degrade the siRNA.

To clear these two hurdles, Robertson and his team engineered hollow nano-sized particles — nanoliposomes — from globes of fatty acids into which they packed the siRNA. Next, the researchers used a portable ultrasound device to temporarily create microscopic holes in the surface of the skin, allowing the drug-filled particles to leak into tumor cells beneath.

“Think of it as tiny basketballs that each protect the siRNA inside from getting degraded by the skin,” explained Robertson. “These basketballs fall through the holes created by the ultrasound and are taken up by the tumor cells, thereby delivering the siRNA drug into the tumor cells.”

When the researchers exposed lab-generated skin — made from human connective tissue — containing early cancerous lesions to the treatment 10 days after the skin was created, the siRNA reduced the ability of cells containing the mutant B-Raf to multiply by nearly 60 to 70 percent, and more than halved the size of lesions after three weeks.

“This is essentially human skin with human melanoma cells, which provides an accurate picture of how the drug is acting,” said Robertson.

Mice with melanoma that underwent the same treatment had their tumors shrink by nearly 30 percent when only the mutant B-Raf was targeted. There was no difference in the development of melanoma when the Akt3 gene alone was targeted, though existing tumors shrank by about 10 to 15 percent in two weeks.

However, when the researchers targeted both the Akt3 and the mutant B-Raf at the same time, they found that tumors in the mice shrank about 60 to 70 percent more than when either gene was targeted alone.

“If you knock down each of these two genes separately, you are able to reduce tumor development somewhat,” Robertson said. “But knocking them down together leads to synergistic reduction of tumor development.”

While human clinical trials could be years away, Robertson says the findings show the promise of personalized medicine, where patients could receive treatments designed to specifically target the errant genes or proteins for their disease.

“The problem with this cancer, like most cancers, is that if you target one protein, the cells quickly find a way around it,” explained Robertson. “Most chemotherapies are ineffective because patients initially respond but then when the tumor reoccurs, the cancer does not respond at all.”

In the future, Robertson believes physicians could identify three or four targets in a patient, which could be treated sequentially or in combination for a greater health benefit.

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Other researchers on the paper include Melissa A. Tran, graduate student, Raghavendra Gowda, postdoctoral fellow, Arati Sharma, assistant professor, and Mark Kester, professor, all in the Department of Pharmacology; James Adair, professor of materials science and engineering; E. J. Park, graduate student, and Nadine Barrie Smith, associate professor of bioengineering, all at Penn State.

The American Cancer Society, The Foreman Foundation for Melanoma Research, and the Department of Defense Technologies for Metabolic Monitoring funded this work.

Source: Amitabh Avasthi
Penn State

People who carry a particular genetic variant are at significantly increased risk of developing malignant melanoma, new research shows.

Melanomas are known to be caused by exposure to the ultraviolet light in sunlight, but the precise mechanisms involved are complex. In a presentation at the 33rd Congress of the European Society for Medical Oncology (ESMO) in Stockholm, Portuguese researchers showed that variations in a gene known as cyclin D1 also increase susceptibility to the disease.

This gene plays a key role in regulating the cell cycle, the intricate molecular process by which cells divide and replicate. Alterations in its activity are known to be associated with the development of several human cancers, including melanoma.

PhD student Raquel Catarino from the Portuguese Institute of Oncology in Porto and colleagues studied a particular variant of the gene in the blood of 1,053 individuals, including 161 cases with melanoma and 892 healthy individuals. Their analysis showed that individuals carrying two copies of the variant were 80% more likely to develop melanoma.

“Our study demonstrates that cyclin D1 polymorphism is associated with a higher risk of melanoma development, indicating that this genetic variation may confer growth advantage to cancer cells. Our results indicate that the proportion of melanoma cases attributable to this genetic alteration is 14%.”

Other research groups have identified other genes that are implicated in susceptibility to melanoma. “We think that once the genetic factors involved in melanoma oncogenesis are identified and their importance established and validated, the individual’s genetic profile could help clinical decisions, including disease screening and selection of higher-risk individuals,” Dr. Catarino said.

In another presentation, Prof. Poulam Patel from Nottingham University in the UK reported the final results from a large randomized phase III study in 859 patients with stage IV melanoma. The clinical trial, coordinated by the EORTC Melanoma Study Group, involving 92 institutions in Europe, the US and Latin America, is the largest of its kind in this group of patients.

In the trial, chemotherapy-naive patients with stage IV disease were treated with either dacarbazine 1000 mg/m2 IV every 21 days (the current standard treatment) or temozolomide 150 mg/m2 orally on days 1 - repeated every 14 days. “Temozolomide is an oral chemotherapy which has activity against melanoma and this regimen is a dose-intense way of delivering the treatment in the hope of delivering more active drug and more effectively,” Prof. Patel said. “The study showed that although there were small differences in the response rate and side effects, there was no difference in the overall survival or progression-free survival.”

“We continue to look for new treatments that will show benefit when tested in a large phase III study,” he said.

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Source: ESMO Press Office
htEuropean Society for Medical Oncology

Scientists and clinicians from around the world will gather in Philadelphia, Pennsylvania, next week at the American Association for Cancer Research’s third International Conference on Molecular Diagnostics in Therapeutic Development.

The conference is subtitled, “Fulfilling the Promise of Personalized Medicine,” which reflects the potential of molecular diagnostics to provide new strategies for tailoring therapies to fit the needs of each cancer patient’s unique biology.

Sessions will include discussions on the use of biomarkers in clinical practice and new drug development, advanced imaging technologies for diagnosis, and the application of proteomics in personalized medicine.

Novel findings to be reported at the conference include:

• A new gene expression analysis that shows important differences in brain cancer.

• A groundbreaking method of measuring changes in DNA .
• A new biomarker that could more accurately determine the prognosis of patients with head and neck carcinoma.
• A more complete and accurate test for blood disorders.

“As genetic, proteomic, imaging and other new technologies have become more sophisticated and our knowledge of tumor biology and signaling pathways advances, so too does our ability to molecularly characterize individual tumors and identify germ line and somatic determinants of patient prognosis and response,” said conference chairperson Gordon B. Mills, M.D., Ph.D., chairman of the Department of Molecular Therapeutics at the University of Texas M. D. Anderson Cancer Center.

“This new era of personalized medicine has brought with it great opportunities to enhance cancer drug development and improve patient care,” said Mills. “However, in order to harness this potential and maximize these opportunities, it is essential that there be an ongoing exchange of new ideas and information.”

In addition to the symposia and poster sessions, the conference will include two keynote lectures. The first will be from David Sidransky, M.D., director of head and neck cancer research at the Johns Hopkins Hospital, who will deliver, “Personalized Cancer Medicine in the Next Decade.” The second will be from Joe W. Gray, Ph.D., director of the Division of Life Sciences at the Lawrence Berkley National Laboratory, who will speak on, “Models of Molecular Diversity to Facilitate Marker Guided Therapy.”

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The AACR’s third International Conference on Molecular Diagnostics in Cancer Therapeutic Development will be held September 22-25, 2008, at the Downtown Marriott in Philadelphia. For more information about the conference, please visit: http://www.aacr.org/page14221.aspx.

The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is the only journal worldwide dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

Source: Jeremy Moore
American Association for Cancer Research

Scientists at The University of Nottingham have isolated three important genes involved in the development of a type of childhood brain cancer. The breakthrough is revealed in a study published in the British Journal of Cancer.

Researchers from the Children’s Brain Tumour Research Centre at The University of Nottingham, on behalf of the Children’s Cancer and Leukaemia Group (CCLG), have found three genes associated with specific characteristics of ependymoma the third most common form of childhood brain cancer.

Before now, relatively little was known about the underlying biology of this disease. The results of this study provide a more detailed understanding of the genetics behind ependymoma, which could help scientists develop targeted drugs to treat the disease more successfully, and with fewer side effects.

Around 35 children are diagnosed with ependymoma each year in the UK, and around half of these will be under three years old. In total, around 300 children under 15 are diagnosed with a brain tumour each year in the UK.

Overall, three quarters of children with cancer in the UK can be successfully treated, but survival for ependymoma is just 50 per cent. And around half the children who are initially successfully treated will suffer a relapse of the disease.

Lead author Professor Richard Grundy from the Children’s Brain Tumour Research Centre at The University of Nottingham, said: “Understanding the biological causes of cancer is vitally important as it will help us to develop drugs that target abnormal genes in cancer cells but not in healthy cells, which is what traditional chemotherapy treatments do. More accurately targeted treatments will cause fewer side-effects than conventional chemotherapy and be more effective. So this is an important finding which we hope will lead to the development of new treatments for ependymoma.”

The team analysed the genome wide expression pattern of ependymoma identifying three genes with distinct profiles. They confirmed the involvement of these different genes in 74 samples of ependymoma. From this they discovered that a gene called SI00A4 was strongly associated with tumours in very young children. SI00A6 was a marker of a tumour in a specific part of the brain and high levels of CHI3L1 was common in cancers showing a larger degree of cell death.

The genes discovered are all located on a section of Chromosome 1 that this research group had previously linked to poor survival for ependymomas.

Professor Grundy added: “We hope our findings will lead to a more detailed understanding of ependymoma. This is crucial if we are to ensure each child receives the most appropriate treatment for their disease and that we reduce the number of children in which their cancer recurs.”

Kate Law, director of clinical trials at Cancer Research UK, which is the major funding provider of the CCLG, said: “Relatively little is known about the causes of childhood cancer, so this is an important study. Overall survival rates for children’s cancers have been rapidly improving thanks in part to international clinical trials but it’s crucial that research like this takes place to improve treatments even further.”

NOTTINGHAM UNIVERSITY
University Park
Nottingham
NG7 2RD
http://www.nottingham.ac.uk

For patients with chemotherapy-induced anemia, adding intravenous iron to treatment with the drug darbepoetin alfa results in a faster and more potent improvement in response with lower doses of the drug, according to data presented at the 33rd Congress of the European Society for Medical Oncology (ESMO) in Stockholm.

Anemia is a common problem in cancer patients, caused by a combination of factors including the malignancy itself, plus the effects of chemotherapy. Treatments can include drugs such as darbepoetin alfa, which stimulates the production of new blood cells, although up to one in three patients do not respond to these therapies.

Dr. Michael Auerbach, a hematologist from Baltimore, Maryland, USA, and colleagues studied whether adding intravenous iron would improve response rate in a group of 238 patients with a range of cancer types. The researchers divided the patients into four groups: either high-dose darbepoetin alfa plus or minus iron, or low-dose darbepoetin alfa plus or minus iron.

“In a large subset of patients with cancer-related anemia, an important factor that limits their response to treatment is the presence of an iron deficiency,” Dr. Auerbach said.

The results of the 18-week trial showed that adding intravenous iron, administered every three weeks, improved the likelihood that patients achieved the target for hemoglobin levels, and reduced the length of time it took to see an improvement in the production of red blood cells, Dr. Auerbach reported. The results held true for either dose of darbepoetin alfa.

Other studies have shown that adding intravenous iron can have a similar impact with other erythropoiesis drugs, he noted. “This is the sixth of six studies to show it. They all decreased the need for erythropoiesis stimulating agents–for the same benefit with huge cost savings and probable decreased toxicity.”

EUROPEAN SOCIETY FOR MEDICAL ONCOLOGY (ESMO)
Via la Santa 7
6962 Viganello-Lugano
http://www.esmo.org