BACKGROUND AND CHALLENGES

In 2009, more than 44,000 new cases of leukemia were estimated in the United States, and nearly 22,000 deaths were expected to occur. Leukemia is the Number One cause of cancer deaths among children under age 15, accounting for more than 30% of all cancer deaths in this age group. Although these numbers are still daunting, the outlook for patients with leukemia is much better now than thirty years ago. In the mid-1970s, only 35% of patients suff ering from leukemia experienced five year survival.

Today, that number has increased to 50%. It cannot be forgotten that much of the improvement in patient survival was made possible by the continuous development of new and more eff ective anti-cancer treatments, which was largely driven by the rapid advancement of cancer research and the application of new technologies in oncology.

Achieving further advances in clinical care for this devastating disease will require continuous support of creative new research approaches - research that will enlarge our understanding of the disease process in leukemia and lead to more effective strategies for leukemia treatment and prevention. In 2010, NFCR continues to fund several leukemia
research projects, each led by a pioneer in the field. Through their efforts to develop reliable diagnostic tools for tailoring treatment to individual patients, explore novel strategies to treat leukemia more effectively, and develop innovative approaches to conquering the complications of bone marrow transplantation for leukemia patients.

National Foundation for Cancer Research scientists are mounting a solid attack on this deadly cancer. This is the type of innovative research that may well produce new methods of saving and extending the lives of leukemia patients. Listed below are a few notable research programs that NFCR funds.

FUNDING INNOVATION

Tailoring a new anti-cancer drug to the right patients.
Alan Sartorelli, Ph.D., Yale University School of Medicine

CloretazineTM (now named OnriginTM) is a new anti-cancer drug developed by NFCR Scientist Alan Sartorelli, Ph.D.  Cloretazine is currently being evaluated in late stage clinical trials for the treatment of Acute Myeloid Leukemia (AML), one of the most common types of leukemia in adults. In a phase II clinical trial in elderly patients with relapsed AML, about 30% of the patients had a complete response to Cloretazine - meaning that the drug was so effective that all signs of cancer disappeared in those patients following treatment.

These results were impressive, but they also suggested that Cloretazine is unlikely to bring uniform benefits for all AML
patients. Consequently, understanding how to predict which patients are most likely to benefit from treatment with Cloretazine has become one of the most vexing questions facing the clinicians treating those patients, and that is now the focus of Dr. Sartorelli's research team.

At the molecular level, Cloretazine works best in tumor cells which contain low levels of a protein called AGT. Because AGT levels vary greatly in individual patients' tumors, a reliable method of measuring the level of AGT in tumor tissue would be an effective way for physicians to predict which patients will most likely respond to Cloretazine and those
who probably will not. To be clinically applicable, the method must be both accurate and simple to carry out. Taking advantage of the drug's molecular mechanism, Dr. Sartorelli has recently developed an AGT assay that meets both criteria when tested with tumor cell cultures. Dr. Sartorelli is now further evaluating the AGT assay with human tumor samples, and this new method may soon be used in the clinic, enabling physicians to target the use of this drug to the most appropriate of their leukemia patients.

Developing novel immunotherapy to treat Leukemia and Lymphoma
Laurence J. N. Cooper, M.D., Ph.D., M.D. Anderson Cancer Center

Cancer cells, although much different from normal, healthy cells, are often able to elude the human body's immune surveillance system. NFCR Scientist Laurence J.N. Cooper, M.D., Ph.D., and his research team in Houston have developed a cutting-edge technique that improves the ability of the human immune system to fight cancer. With this new technique, Dr. Cooper's team is able to engineer immune cells (T cells), enabling them to detect a molecule called CD19 which is expressed on the cell surface of certain types of leukemia and lymphoma.

Once engaged with their targets, these "upgraded" T cells will then mount full blown attacks to eliminate those cancer cells. Th is novel immunotherapy is currently being evaluated in a Phase I clinical trial in patients with CD19+ lymphoma. If successful, it may soon be tested for treatment of patients with leukemia, providing oncologists with a powerful new weapon to fight this disease. Currently, Dr. Cooper continues to explore more cost-effective ways to engineer the immune cells, which is crucial for large-scale clinical application of this novel therapy.

Conquering the lethal complication of bone marrow transplantation
Curt Civin, M.D., University of Maryland School of Medicine

Bone marrow transplantation is a life-saving procedure used in patients with leukemia and other diseases to replenish their vital blood-forming system, which is often destroyed by high-dose chemotherapy treatment. However, the very same procedure may cost a patient's life if a severe complication known as the graft-versus-host disease (GVHD) occurs. When a patient receives a bone marrow transplant from a donor (allogeneic transplant), a subset of the immune cells from the transplant can be activated to mount vigorous immunologic attacks on the patient's (the recipient's) tissues, causing GVHD.  This side effect could be lethal, which greatly limits the clinical application of allogeneic bone marrow transplantation.

NFCR Fellow Curt Civin, M.D., and his team (formerly at the Johns Hopkins University School of Medicine) developed a unique strategy which sends the anti-recipient immune cells onto a suicidal path, while keeping intact the "recipient-friendly" cells from the transplant, which is essential for successful blood replenishment in the patient. Dr. Civin hopes to bring this promising treatment strategy into the clinic for further evaluation in the near future.

Developing a new class of multi-functional anti-cancer drugs
Michael Sporn, M.D., Dartmouth Medical School

NFCR Project Director Michael Sporn, M.D., is widely recognized as a leader in the fi eld of new anti-cancer drug development. Dr. Sporn and his team of researchers have synthesized a new class of anti-cancer drugs called synthetic triterpenoids which have shown powerful preventative or treatment eff ects against leukemia and other types of cancer.

Triterpenoids are naturally synthesized in many plants, and some of them have been found to have weak anti-infl ammatory and anti-cancer activity. Dr. Sporn and colleagues at Dartmouth Medical School hoped to generate a class of synthetic triterpenoids which would have more powerful anti-inflammation and anti-cancer properties than their naturally-occurring counterparts. Through a complex and original process of chemical analysis, compound synthesis and biological evaluation, the team developed and refi ned a small group of synthetic triterpenoids (including CDDO, CDDO-Im, and CDDO-Me) that have shown potent, multi-functional activity in the cell. Depending on the dose, these compounds can suppress infl ammation, inhibit cancer cell proliferation, and induce cancer cell suicide in a variety of cancer cell lines. These properties are important for prevention and treatment of multiple cancer types, including leukemia.

Currently, two of the synthetic compounds have already entered Phase I clinical trials for treatment of patients with leukemia and solid tumors. Following further laboratory and clinical testing, this new class of anti-cancer compounds may soon reach patient bedsides for prevention and treatment of a variety of cancers.

NEXT STEP: HOW YOU CAN HELP

These NFCR-supported research projects hold great promise for yielding more eff ective therapies for leukemia. With more money, however, they could ramp up their efforts and accelerate progress. That is what the urgent plight of leukemia patients demands, and that is what we at NFCR are committed to making possible. Your contribution will be directed to these and other life-saving NFCR research initiatives against leukemia.  To make a donation, click here.