Therapies for ALL and AML targeting MER receptor hold promise of more effect with less side-effect

March 11, 2013

Two University of Colorado Cancer Center studies show that the protein receptor Mer is overexpressed in many leukemias, and that inhibition of this Mer receptor results in the death of leukemia cells - without affecting surrounding, healthy cells.

The first study, published today in the journal Oncogene, worked with acute myeloid leukemia (AML), for which current chemotherapies offer a cure rate of only about 55 percent.

"In about 2/3 of all AML patients and about 90 percent of adult AML patients, we found that the Mer receptor was upregulated. Mer receptor protein shouldn't exist in normal myeloid cells, but we found it abnormally expressed," says Doug Graham, MD, PhD, investigator at the CU Cancer Center and associate professor of pediatrics and immunology at the University of Colorado School of Medicine.

The Mer receptor sits within the cell membrane, and when it becomes activated the cell receives signals to grow and survive. Leukemia and perhaps many solid cancers have taken advantage of Mer's cell survival function to assist the cancer's rampant proliferation. When Graham and colleagues used shRNA to silence the production of Mer in leukemia cells, they showed decreased leukemia cell survival, increased sensitivity to existing chemotherapies and longer survival in mouse models of leukemia.

A second study, published this month in Blood Cancer Journal, shows similar results with acute lymphoblastic leukemia (ALL), the most common pediatric cancer.

"The ALL cure rate is already over 80 percent, but for patients who relapse, the prognosis is much less optimistic. We need targeted therapies to use as second-line treatments for the population for whom existing therapies aren't lasting, particularly in patients with relapsed T cell ALL," Graham says.

Second, he points out that a quarter of pediatric ALL patients who respond to existing chemotherapies do so at the price of significant long-term side-effects. "And so in addition to increased survival, the second goal of targeted therapies is decreased side-effects," Graham says.

Inhibition of the Mer protein receptor is promising on both accounts.

"Not only do B-cell and T-cell leukemia cells die when you knock down Mer receptor expression, but these cells are also much more sensitive to existing chemotherapies. By hitting Mer, we're making the chemotherapy more effective," Graham says.

In ALL and AML, Graham's studies show that making Mer inhibition means that less chemotherapy may have equal or stronger effect. Strong preliminary evidence shows that Mer may be the key to less toxic, more effective therapies for leukemia.
-end-


University of Colorado Anschutz Medical Campus

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.