Cancer Researchers Discover Genes that Can Determine How Patients Respond to Pre-Leukemia Drug
News Mar 27, 2008
A team of cancer researchers at Manhattan-based St. Vincent’s Comprehensive Cancer Center, in partnership with the Broad Institute of MIT and the Dana Farber Cancer Institute in Boston, has identified 30 red cell-related genes which determine the effectiveness of using the drug Revlimid® (lenalidomide) on patients with pre-leukemia, known as Myelodysplastic Syndrome (MDS).
The discovery was recently reported in the on-line journal PLoS Medicine.
Nearly 20,000 Americans are diagnosed annually with MDS. While most are men over 65 years old, women, young people and children also develop MDS. The causes have not been determined, although those who have worked with certain chemical compounds, especially benzene, had exposure to radiation or chemotherapy treatments, or have certain genetic conditions, including Downs Syndrome, are considered to be at high risk.
Of those diagnosed, one-third develop acute myelogenous leukemia (AML). Cure rates for AML range from 20 – 45% in clinical trials, although these results are skewed by a disproportionate number of younger people who participate in the trial and are more likely to tolerate aggressive treatments.
“A derivative of the drug thalidomide, Revlimid is FDA-approved for the treatment of transfusion-dependent anemia in patients with lower risk MDS who carry a specific chromosomal abnormality,” says Azra Raza, M.D., attending physician and head of the MDS program, St. Vincent’s Comprehensive Cancer Center, senior and corresponding author of the study.
“This study shows the determinant of Revlimid’s effectiveness to be 30 red cell-related genes that are consistently under-expressed, irrespective of the chromosomal abnormality.“
“The research extends the findings of a multi-center trial which we reported in the January 1, 2008 edition of the journal Blood,” notes Naomi Galili, Ph.D., director of St. Vincent’s Bone Marrow Translational Laboratory. “That study showed Revlimid therapy eliminated the need for blood transfusions among 26% of MDS patients without the chromosomal abnormality. We postulated those patients must share some other genetic profile, which led us to the discovery of the 30 under-expressed red cell-related genes.”
“The use of genetic testing in MDS to determine how individuals will respond to specific drug therapies not only keeps patients from getting a drug like Revlimid that won’t benefit them, but also means they won’t be exposed to its potentially toxic side effects,” says Dr. Raza. “It is a win-win for patients who receive better care, their doctors with a quest for better outcomes, and insurers, who won’t have to pay for expensive drugs and ineffective treatments.”
Stereochemistry is a science of reflection. Two chemical molecules with the same composition and structure, but with one as the mirror image of the other, can produce wildly varying effects. But University of Utah chemist Matt Sigman has been developing a way to get a better grasp on this tricky field of chemistry.READ MORE