Featured Research

from universities, journals, and other organizations

Novel, Even Unlikely Drugs May Curb Childhood Leukemia

Date:
May 21, 2001
Source:
Childrens Hospital Of Philadelphia
Summary:
While survival rates for childhood leukemias have soared in the past 30 years, about a quarter of pediatric cases remain stubbornly resistant to treatment. As a new attack strategy, scientists are adapting recent discoveries about cell development to coax leukemia cells back to normal growth patterns or to reprogram them into committing suicide.

Philadelphia, Pa. -— While survival rates for childhood leukemias have soared in the past 30 years, about a quarter of pediatric cases remain stubbornly resistant to treatment. As a new attack strategy, scientists are adapting recent discoveries about cell development to coax leukemia cells back to normal growth patterns or to reprogram them into committing suicide.

"Reaching the next level of leukemia treatment will require many new approaches that draw upon our expanding knowledge about how healthy cells differentiate during normal growth and development," said Beverly Lange, M.D., director of experimental therapeutics within the Division of Oncology at The Children’s Hospital of Philadelphia, who is an expert in these new attack strategies.

Unlike conventional cancer drugs, the newer drugs are based on detailed knowledge of cellular mechanisms that can be used to manipulate cancer cells in a way that is gentler to surrounding healthy cells.

Oncologists at Children’s Hospital are investigating a number of novel, even unlikely, drugs as highly specific, less toxic weapons against childhood leukemia. For example:

-- A form of vitamin A is being used to reprogram a cancer cell into becoming a harmless, normal white blood cell.

-- Borrowing from its use in traditional Chinese medicine, carefully controlled doses of arsenic can trigger cancer cells to commit suicide by mimicking the normal developmental process of "apoptosis," or programmed cell death.

-- A new type of leukemia drug, the bioengineered compound Glivec, can block the genetic signals that direct cancer cells to grow, while leaving normal cells largely unharmed.

-- The naturally occurring protein interleukin-2 may kick-start the body’s immune system to better fight leukemia.

Taming cancer cells

Some experimental new treatments rely on methods that neutralize or disrupt cancer cells rather than killing them outright in a frontal attack. "Most conventional cancer drugs rely on lysis, in which a direct attack by the drug causes the cancer cell to burst and die," Dr. Lange explained. But cells may also die through indirect methods that target cancer cells while sparing normal cells.

One such method is terminal differentiation, in which a cell enters a mature stage, with a limited lifespan. For example, all-trans-retinoic acid, a form of vitamin A, is used in this way against the diseased blood cells found in acute promyelocytic leukemia (APML). Rather than directly killing the cancer cell, all-trans-retinoic acid forces the cell to differentiate into a mature white blood cell by reprogramming its genetic mechanisms. It redirects the cancer cell into behaving like a normal blood cell rather than an immortal, constantly dividing cancer cell. "At the same time it dooms the cell, because mature white blood cells live for only 12 hours," said Dr. Lange.

Arsenic and cell suicide

When all-trans-retinoic acid does not work against APML, low doses of arsenic may be helpful, using a different cellular mechanism. By targeting a receptor on the surface of the cancer cell, arsenic triggers the process of "apoptosis," or programmed cell death.

This suicide apparatus resides in all cells as a set of proteins that remain dormant until set in motion by molecular signals specific to each type of cell. In early embryonic development, apoptosis sculpts tissues by eliminating unneeded cells. Throughout life, it serves to destroy diseased or nonproductive cells. However, cancer cells may fail to respond to apoptosis signals and become immortal and deadly.

Arsenic can reset the genetic machinery, permitting apoptosis to seal the fate of cancer cells. At the same time, the low dose of arsenic spares healthy cells. Both arsenic and all-trans-retinoic acid are derived from compounds used in traditional Chinese medicines. "Although APML is a relatively rare disease," said Dr. Lange, "these treatments may be useful in other cancers as well."

Blocking cancer signals

News reports over the past year have heralded highly encouraging results from clinical trials of Glivec (STI-571) for adults with chronic myeloid leukemia (CML). Glivec represents a new class of drugs called signal transduction inhibitors that block the signaling pathways that cause cancer cells to grow. It is bioengineered to zero in on a cell receptor present in leukemia cells that carry a genetic defect called the Philadelphia chromosome.

This targeted approach causes minimal side effects to healthy tissue. While CML is rare in children, the same genetic defect found in CML, the Philadelphia chromosome, occurs in an aggressive form of childhood acute lymphoblastic leukemia (ALL).

Directed by Dr. Lange, Children’s Hospital is testing Glivec against that treatment-resistant form of ALL. Through its participation in the Children’s Oncology Group, a collaborative national organization that pools data and expertise from many cooperating cancer centers, Children’s Hospital is currently conducting pediatric trials of the drug. Because studies have suggested Glivec may have wider applications against other types of cancer, Children’s Hospital will test it later this year in children with highly malignant brain tumors.

Boosting immune effects

Also under the umbrella of the Children’s Oncology Group, Dr. Lange is leading tests of interleukin-2 (IL-2), a compound that occurs naturally in the body. IL-2 is an immune system protein that plays an important role in an immune response that occurs after a bone marrow transplant. In the "graft vs. leukemia effect," IL-2 stimulates the body’s natural killer cells to attack leukemia cells and drive the disease into remission.

The pediatric clinical trials led by Dr. Lange will test whether providing IL-2 can confer this benefit against acute myeloid leukemia (AML) in the absence of a marrow transplant. If so, said Dr. Lange, the approach may help children with AML who do not have a sibling donor for a transplant.


Story Source:

The above story is based on materials provided by Childrens Hospital Of Philadelphia. Note: Materials may be edited for content and length.


Cite This Page:

Childrens Hospital Of Philadelphia. "Novel, Even Unlikely Drugs May Curb Childhood Leukemia." ScienceDaily. ScienceDaily, 21 May 2001. <www.sciencedaily.com/releases/2001/05/010521071538.htm>.
Childrens Hospital Of Philadelphia. (2001, May 21). Novel, Even Unlikely Drugs May Curb Childhood Leukemia. ScienceDaily. Retrieved September 1, 2014 from www.sciencedaily.com/releases/2001/05/010521071538.htm
Childrens Hospital Of Philadelphia. "Novel, Even Unlikely Drugs May Curb Childhood Leukemia." ScienceDaily. www.sciencedaily.com/releases/2001/05/010521071538.htm (accessed September 1, 2014).

Share This




More Health & Medicine News

Monday, September 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins