Forgotten side of the Iraq war: shortage of meds for cancer patients

This interesting (and sad) letter in the New England Journal of Medicine highlights the shortage of chemotherapy treatments for children suffering from leukemia:

"There was a significant inverse relationship between the amount of prescribed chemotherapy that was administered and the risk of relapse."

The study reinforced the notion that the most important factor in improving survival, even in children with leukemia, is adequate treatment.

Cancer: tracking progress for the treatment of CML

This fascinating short video interviews some of the top leukemia doctors around the world and looks at how tracking faulty chromosomes is now routine for people with chronic myeloid leukemia. Experts such as Dr Brian Druker and Prof. John Goldman explain what sophisticated laboratory tests can tell about treatment success:

Video

Precise location of an oncogene may determine the onset of childhood leukemia

The white blood cells in our body combat foreign intruders, such as viruses and bacteria. In leukemia, the formation of white blood cells goes haywire and the cells that should develop into white blood cells multiply out of control without fully maturing. This process disrupts the production of normal blood cells, making patients more susceptible to infections. T-ALL, a particular form of leukemia, is the most prevalent cancer in children under 14 years of age and occurs predominantly between the ages of two and three.

With intensive treatment involving chemotherapy, over half of children are cured. But scientists hope to be able to develop targeted therapies that are less toxic than chemotherapy, based on knowledge of the biological processes behind T-ALL.

Oncogenes are often at the root of cancer. Scientists around the world are theefore concentrating on identifying oncogenes and their related proteins. Recent research by the Flanders institute of Technology in Belgium (VIB-K.U.Leuven) indicates that the location in the cell where these proteins are found plays an important role in the entire carcinogenic mechanism.

In collaboration with the Nederlands Kanker Instituut, Amsterdam and Harvard Medical School, Boston, the VIB researchers have demonstrated that NUP214-ABL1, a fusion of two proteins, is carcinogenic only when it is in a protein complex near the nucleus of the cell. Located at another place in the cell, NUP214-ABL1 does not lead to cancer. This finding sheds new light on the study of carcinogenic processes.

Many forms of cancer are caused by genetic defects in which a certain kinase becomes too active and this is the case with NUP214-ABL1. The most obvious solution is to make the carcinogenic kinase inactive, and so kinase inhibitors are usually used to combat these kinds of cancers. However, the carcinogenic kinase often becomes resistant to these inhibitors, which is certainly true for T-ALL. new approaches are therefore being actively sought.

The recent research results now offer a possibility. It has been shown in cells that NUP214-ABL1 is no longer carcinogenic when it cannot bind with the protein complex in the vicinity of the cell nucleus. On the basis of these results, the researchers want to further investigate the therapeutic possibilities of compounds that render binding between the complex and NUP214-ABL1 impossible. This study also indicates that the location of proteins can play an important role in other forms of cancer/leukemia as well.

Stand Up to Cancer!

Stand Up To Cancer, a new initiative to raise philanthropic dollars for accelerating ground-breaking research, launched recently through a large collaboration uniting the major television networks, entertainment industry executives, celebrities and prominent leaders in cancer research and patient advocacy.

ABC, CBS and NBC will donate one hour of simultaneous commercial-free prime time for a nationally televised fund raising event to air on September 5, 2008 (8 pm EDT and PDT), aimed at rallying the public around the goal of ending cancer's reign as a leading cause of death.

In addition to the nationally televised network fundraising event, other key elements of the initiative include:

Standup2cancer.org

With both interactive applications and rich content, the SU2C website will foster an online community for everyone affected by cancer, utilizing the same approach as the televised special: it will move, educate and even entertain users. Features include: The Constellation: For a dollar donation or more, users can launch a star in honor of anyone who has received a cancer diagnosis.

The Stand: An interactive Facebook application to illustrate that the ‘cancer community' encompasses everyone and that we are all connected by this disease. SUTV: Features video segments rich in scientific and research information, as well as ones that confront the personal and human side of cancer's impact. SU2C Magazine: Offers seven sections of diverse content written by leading voices in every field.

Public Service Announcement (PSA) Campaign

A series of TV, radio and print PSAs featuring celebrities and members of the general public to mobilize support for the campaign will air and appear in publications.

Leukemia drug may influence stroke

A drug called tPA has proven its value as the most effective emergency treatment for a common kind of stroke over the last decade. Its effectiveness is limited by two factors: tPA can cause dangerous bleeding in the brain and its brain-saving power fades fast after the third hour of a stroke.

A new paper published online in Nature Medicine reveals why tPA has these limitations. It also gives tantalizing evidence about how those problems might be overcome, if a stroke victim first takes a drug currently used to treat leukemia.

The researchers, from the University of Michigan and the Ludwig Institute for Cancer Research (LICR) Stockholm Branch at Karolinska Institutet emphasise that it's still too early to apply their findings from mice to the treatment of stroke victims everywhere.

A clinical trial will begin soon to test the theory in humans, using the leukemia drug imatinib (Gleevec). In mice, that drug greatly reduced bleeding, even if tPA wasn't given until five hours after a stroke began.

tPA apparently increases the risk of bleeding and leakage of fluid within the brain, by accident. The drug has a tendency to act upon a protein known as PDGF-CC, and the PDGF-alpha receptor that it binds to. This interaction causes the usually impervious "blood-brain barrier" to become porous, leading to leakage. Gleevec inhibits the PDGF-alpha receptor, potentially counteracting tPA's effect.

The trial results are awaited with anticipation... If these findings are confirmed in humans, Gleevec could be given immediately when a stroke is suspected to extend the window in which tPA may be given.

Knocking out cancer cells in Leukemia

Cancer initiating cells (CICs) or leukemia initiating cells (LICs) are stealth populations impervious to conventional chemotherapy and resistant to targeted cancer therapies. When a leukemia patient relapses following a period of remission, it is the LICs that are the cause of the disease’s re-emergence.

Researchers at the Beth Israel Deaconess Medical Center (BIDMC) have found that a tumour suppressor protein known as PML appears to be the factor that enables LICs to maintain their quiescence, the inert state that protects them from being destroyed by cancer therapies. They suggest that inhibition of PML is a promising target for new agents.

Their findings, which appear in Nature, also demonstrate that PML can be degraded with an arsenic-based agent called arsenic trioxide, which has been used in traditional Chinese medicine. When combined with chemotherapy, the arsenic-based therapy, already proven safe and non-toxic in clinical trials for a rare form of leukemia called Acute Promyelocytic Leukemia (APL) can also potentially treat the more common Chronic Myeloid Leukemia (CML) and reduce risk of relapse.

The concept is a very simple one; 90% of existing cancer treatments are anti-proliferative agents. They target the pool of proliferative cells, leaving behind the dormant LICs. By knocking out the quiescent cells with arsenic trioxide, the risk of relapse is much reduced. This approach might be useful in other treatment approaches for different leukemias.

Cancer intelligence - cytogenetic abnormalities in AML

Cytogenetic abnormalities are long been useful in guiding treatment for acute myeloid leukemia (AML). One of the crucial questions in the treatment algorithm is whether or not an allogeneic stem-cell transplant is an option. Transplantation can be a curative treatment for AML, but it carries risks, including transplant related mortality and morbidity. Currently, it is usually considered for AML when the cytogenetic abnormalities foretell a high risk for relapse after chemotherapy and avoided when there is a cytogenetic pattern that is associated with a relatively favorable prognosis.

New details of differences among patients with cytogenetically normal AML, which appear to affect both clinical and treatment outcome, are described in 2 papers published in the May 1 issue of the New England Journal of Medicine. One paper describes new gene mutations, and the other outlines microarray microRNA expression profiles. Both studies demonstrate the complex molecular heterogeneity of AML and may add to the accumulating knowledge about the way genetic disruptions in AML can affect prognosis.

Oncology news - lowering risk for leukemia

A new analysis of published studies has found that children who attended day care or playgroups had about a 30% lower risk of developing acute lymphoblastic leukemia (ALL) than children who did not.

ALL is the most common type of childhood leukemia, accounting for more than 80% of cases, and typically occurs in infants between the ages of 2 and 5 years. It is one of the most common cancers in children in the industrialized world, affecting about 1 in 2000 children.

One theory about how the disease develops focuses on early infection. Some proponents of this theory believe that if the immune system is not challenged early in life and does not develop normally, then it mounts an inappropriate response to infections encountered later in childhood, the charity explains. This could provoke the development of leukemia in children who are susceptible, for example, because of a genetic mutation.

Children who attend day care and playgroups are likely to be exposed to common infections early in life; such environments are known to increase the spreading of infection. The latest finding supports the theory that early exposure to infection offers some protection against the disease.

The analysis included 14 published studies and involved 6108 children with and 13,704 without leukemia. Parents were asked about day care and playgroup attendance and other forms of social interaction. Twelve of the studies showed that social interaction had a protective effect against leukemia and 2 showed no effect. Overall, the risk for leukemia was lowered by about 30%. This remained the case when the researchers re-analysed the data and considered only children who had attended day care before the age of 2 years. When 5 studies were excluded because of concerns about the methodology that had been used, analysis of the remaining 9 studies found that the risk for leukemia was lowered by 40%.

Source: 2nd Children with Leukaemia Causes and Prevention of Childhood Leukemia Conference. Presented April 29, 2008.