Targeting BCR signaling pathway

April 5, 2010

This recent news items nicely describes the BCR signaling pathway and how

drugs may be used to target it. We have also included a query of studies of

a drug that is thought to target this pathway - Dasatinib.

Karl

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Gene Mutations Reveal Potential New Targets for Treating aggressive form of

" When a normal B cell encounters a foreign substance, proteins on the cell

surface known as B cell receptors (BCR) activate signaling pathways that

tell the cell to survive and proliferate.

A signaling pathway is a stepwise series of biochemical events that help

regulate important cellular functions, such as proliferation and survival.

Each pathway contains points at which normal signaling can become altered,

causing cells to function abnormally. Alterations in signaling pathways have

been found in many types of cancer cells. Previous research had suggested

that BCR signaling might contribute to the development of lymphomas;

however, direct genetic and functional evidence was lacking.

In the new study, researchers first used advanced laboratory techniques to

identify critical points in the BCR signaling pathway that affect the

survival of lymphoma cells. They found that interference with several

individual components of this pathway caused lymphoma cells to die. Thus,

ongoing BCR signaling -- which the authors refer to as chronic active

signaling -- is necessary for ABC subtype DLBCL cell survival.

.. the Staudt team found that dasatinib, a drug that is approved for the

treatment of chronic myelogenous leukemia, could turn off BCR signaling by

inhibiting the activity of one of the pathway's components, a protein called

BTK, thereby killing ABC subtype DLBCL cells that exhibit chronic active BCR

signaling. "

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Clinical trials: Dasatinib and NHL OR CLL http://bit.ly/a5HDEd

All the best,

~ Karl

Patients Against Lymphoma

Patients Helping Patients

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