Gene blockage may help treat childhood cancer (Reuters Health - 14/04/2008) 

Overactivity of a gene called ODC1 is associated with poor survival of neuroblastoma, a common, often fatal cancer seen mostly in young children, according to research presented Sunday at the American Association for Cancer Research 2008 meeting in San Diego. The good news, however, is that blocking this gene may improve outcomes. In the study, the researchers gave an ODC1-blocking drug called DFMO to mice with the disease and actually 
cured some of them. Dr. Michelle Haber of the Children's Cancer Institute Australia in Sydney and colleagues analyzed neuroblastoma specimens from 209 patients before treatment and found that ODC1 overactivity predicted poor outcomes. "Patients with low levels of ODC1 in their tumors had significantly better survival," Haber told the conference. Moreover, patients with a variant of ODC1 associated with lower activity had better outcomes than patients without this variant, she reported. "We've shown that ODC1 is a good target in primary neuroblastoma because the higher the levels of this gene, the worse the patients do," Haber said.
Haber's team also showed that inhibition of ODC1 with DFMO delayed or prevented the development of neuroblastoma in mice. "Most importantly," Haber said, the findings demonstrate that the effectiveness of standard chemotherapy drugs can be substantially improved by adding DFMO. In fact, when DFMO was 
combined with the chemotherapy drug cyclophosphamide, a number of the mice were cured of their cancer. These findings suggest there is a new treatment approach for this childhood cancer, which has a very high relapse rate, she concluded.

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Cancer survivors' follow-up care falls short -(USA Today) 

A new study shows that most pediatric cancer survivors aren't getting key follow-up treatment as adults. 12% Haven't seen a doctor in the past two years
68% Got no follow-up care related to their pediatric cancer. Top cancer researchers are gathered at the American Society of Clinical Oncology annual meeting in Chicago. Most childhood cancer survivors aren't getting important follow-up care to prevent serious long-term side effects of their treatment, a new study shows.Experts note that progress against pediatric cancers has come at a high price. Although about 80% of children with cancer are cured of their disease, nearly two-thirds later develop a chronic health problem related to their tumors or therapy, says Paul Nathan, an oncologist at the Hospital for Sick Children in Toronto and the study's lead author.

Certain patients face especially high risks. Up to 20% of girls and young women treated with chest radiation — a common treatment for Hodgkin's disease — will develop breast cancer as a result, says Nathan, who presented his research Sunday at the American Society of Clinical Oncology meeting in Chicago. And up to half of children treated with high doses of anthracycline-based chemotherapy will develop heart problems, Nathan says. For these reasons, experts recommend all cancer survivors at risk of heart disease have a test called an echocardiogram every one to two years, Nathan says. Those at risk of breast cancer should have yearly mammograms beginning at age 25, which is 15 to 25 years earlier than typically recommended. 

In Nathan's study, however, 28% of those at risk of heart disease got recommended echocardiograms. Only 49% of women at risk of breast cancer received recommended mammograms. Men were less likely than women to get cancer-related screenings; uninsured patients were three times as likely to miss suggested tests, according to his analysis of the 8,522 patients in the Childhood Cancer Survivor Study, which tracks adults who were treated for pediatric cancer between 1970 and 1986. Patients in the study had a median age of 7 when they were diagnosed with cancer. Their median age today is 31. Nathan says he was disappointed in the findings. And he notes that his study actually may present an overly optimistic picture. Because study participants are more aware than others of long-term effects of cancer, they may be more likely than the average survivor to seek follow-up care. Nathan says the country needs to better educate patients and doctors, many of whom see too few pediatric cancer survivors to be familiar with the latest guidelines for follow-up care. It also would help if insurers paid for crucial follow-up tests for cancer survivors, who need exams more frequently and at younger ages, he says. 

Second cancers are a serious problem in the USA; they account for about 15% of the 1.4 million cancers diagnosed each year, says Patricia Ganz, a professor at the Jonsson Comprehensive Cancer Center at the University of California-Los Angeles. Oncology society president Nancy Davidson, a professor at the Johns Hopkins University School of Medicine in Baltimore, expects the health problems of childhood cancer survivors to increase as patients age. "We're happy with our success, but we have a lot to do to improve our care," Davidson says. 

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Skin cells 'fight child cancer'  

One in 500 children develops some form of cancer. Genetically modified skin cells could be used to fight a cancer which strikes the very young, a UK study suggests. Scientists at UCL said they were able to stimulate the immune system of mice by injecting the animals' skin cells into a neuroblastoma tumour. This type of tumour accounts for 15% of childhood cancer deaths. It is most frequently found in the under-fives. But the authors, writing in the British Journal of Cancer, said clinical trials in humans were at least five years off. 

Nerve cells 

Once the skin cells were genetically modified they became "little factories" producing a sort of protein which helped the immune system, said lead researcher Dr Stephen Hart. This study in mice adds to the growing body of evidence that kick-starting the immune system can work successfully against neuroblastoma 

Dr Bruce Morland 

When they were injected into the tumour site, these cells apparently helped the mouse fight the cancer - with a treated mouse living 90 days or more longer than an untreated mouse. Research in the past has show that genetically modified tumour cells can be turned against the tumour they came from, "but use of the patient's own skin cells would be much easier", Dr Hart wrote. "These cells can be taken by a routine skin punch biopsy, grown in the lab then genetically modified before injecting into the tumour site."  Neuroblastoma is a cancer of specialised nerve cells, called neural crest cells. These cells are involved in the development of the nervous system and other tissues. Prognosis for children diagnosed in the first 12-18 months of life is good, but if it comes back in older children it can be very hard to cure. 

Fewer than 100 new cases are diagnosed each year, according to Cancerbackup. 
Dr Bruce Morland, head of the Children's Cancer and Leukaemia Group, said: "we are delighted that scientists are finding out how to harness the potential of immunotherapy for this childhood cancer. "This study in mice adds to the growing body of evidence that kick-starting the immune system can work successfully against neuroblastoma. "However, we need to learn much more about this approach before we can be sure that it is a safe and effective treatment for children." 

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Gleevec, The Targeted Cancer Pill, Delivers More Good News To Patients- (ScienceDaily - 2/1/2008) 
 

Gleevec, the targeted cancer pill that has saved more than 100,000 lives, now is saving more children with a dire leukemia, as well as preventing disease progression with long term use in adults with chronic myeloid leukemia. "Data at this weekend's meeting continues to show how much Gleevec has completely changed the outlook for so many, many patients facing cancer," said Brian Druker, M.D., director of the OHSU Cancer Institute. At the plenary session of the annual meeting of the American Society of Hematology researchers delivered news that Gleevec has been shown to improve outcomes for children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Ph+ ALL is the childhood leukemia with the worst prognosis and the Children's Oncology Group study shows that adding Gleevec to the treatment almost completely reverses this poor prognosis. The Children's Oncology Group is a worldwide clinical trial cooperative supported by the National Cancer Institute, a branch of the National Institutes of Health.

Also released at the conference is new data from the largest clinical trial in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that showed Gleevec, with long-term use, can prevent progression to advanced stages of the disease. Six-year results of the International Randomized Interferon versus STI571 (IRIS) study for which Druker served as principal investigator, demonstrated that continuous treatment with Gleevec produced a declining rate of relapse over time. The downward trend in the risk of disease progression while on Gleevec has continued since year two of the study. Remarkably, between years five and six, no patients progressed to an advanced phase of the disease.

"The news about Gleevec and the childhood leukemia study as well as the six-year IRIS study that shows there is no progression to advanced phase in CML means that more and more patients are surviving, despite being diagnosed with these cancers," said Druker, JELD-WEN Chair of Leukemia Research, Howard Hughes Medical Institute Investigator and member of the National Academy of Sciences. He also is a professor of medicine (hematology and medical oncology), cell and developmental biology, and biochemistry and molecular biology in the OHSU School of Medicine. Gleevec has also been approved for the treatment of gastrointestinal stromal tumors, pediatric CML, as well as five additional rare cancers. Michael Heinrich, M.D., professor of medicine (hematology/medical oncology) in the OHSU School of Medicine and the Portland Veteran's Affairs medical Center, and a member of the OHSU Cancer Institute, has been the principal investigator in research studies involving GIST and Gleevec.

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Officials backpedal on Pa. cancer study- An abstract making an environmental link to the disease was released by mistake, they say.-(AP) 


Officials yesterday abruptly backpedaled on a federally funded health study that suggested an environmental link to a cluster of rare blood cancer cases in Northeastern Pennsylvania, saying an abstract that made the claim was mistakenly released to the public. The research is to be presented Monday at a medical conference in Atlanta. An abstract released in advance of the meeting said there was "significant evidence" that something in the environment caused an unusually large number of cases of polycythemia vera in Luzerne, Carbon and Schuylkill Counties. The abstract, submitted to the American Society of Hematology, also said people who had lived within 13 miles of a former toxic waste dump in northern Schuylkill County developed the blood cancer at a rate 4.5 times higher than people living in other parts of the three counties.

Steve Dearwent, a government epidemiologist, said that the abstract was written early in the summer and that subsequent analysis of the data did not support the conclusion of an environmental link, although he added that it still was a possibility. He said the abstract should have been revised before it was submitted. "We're going to have to retract the abstract to correct the record because it is erroneous information," said Dearwent, chief of health investigations for the Agency for Toxic Substances and Disease Registry, the federal agency that oversaw the study. "It was preliminary and hadn't been vetted, and unfortunately, it got submitted, unbeknownst to most people here." 

Dearwent said additional research might prove an environmental link. And the study's lead researcher, Dr. Ronald Hoffman of the Mount Sinai School of Medicine in New York, said yesterday that the data do point to something in the environment. "Based upon the data, there's significant concern that there is something in the environment leading to the development of polycythemia vera in that area. The nature of what's causing it is unknown at the moment and is going to require further study," he said. Dante Picciano, a lawyer and geneticist who is active in local environmental issues, said the data indicate a much larger problem than polycythemia vera. He wants study of a wide range of cancers and other diseases in the region. 

"This is the tip of the iceberg. It's inconceivable that you're going to have environmental exposures cause an increase in [only] one type of rare cancer," he said. Polycythemia vera, classified as a cancer, can lead to heart attack or stroke. About one case of polycythemia vera occurs each year for every 100,000 Americans. The cause is unknown. Local activists have raised suspicions about McAdoo Associates, about 80 miles northwest of Philadelphia, where a hazardous waste recycling business operated from 1975 to 1979 and accepted hundreds of thousands of gallons of paint sludge, waste oils, used solvents, PCBs, cyanide, pesticides, and many other known or suspected carcinogens. Environmental officials shut down the site in 1979, and it was later placed on the federal Superfund list and cleaned up. 

Residents fear that chemicals leached into the region's water supplies and polluted private wells and public reservoirs. State and federal environmental officials have said for years that the McAdoo site does not pose a health threat. Activists have also raised concerns about five power plants in Schuylkill County fueled by waste coal and about the practice of filling abandoned coal mines with ash created by coal-burning power plants. In October, officials from the Agency for Toxic Substances confirmed 38 cases of polycythemia vera in the region and said the rate was elevated. At the time, federal officials said there was no proof of an environmental cause, and that cases were scattered throughout the area in no predictable pattern - making the assertions in the abstract surprising.

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