Singapore, Aug 26, 2008: A team of scientists at Cold Spring Harbor Laboratory (CSHL) located at Manhattan, US has published a research identifying an enzyme called Brk that may serve as a target for future drugs developed to fight ErbB2-positive tumors. Researchers claim that Brk helps these tumors become virulent and is also implicated in the process through which the tumors develop drug resistance.

 

“The limited success of existing therapy suggested to us that factors besides ErbB2, or proteins that collude with ErbB2, might nullify the effects of Herceptin and Lapatinib,” explained CSHL Professor, Dr Senthil Muthuswamy, leader of the research team and corresponding author of the paper, published online in the Proceedings of the National Academy of Sciences. Herceptin and Lapatinib are tumor suppressers prescribed in combination with other chemotherapeutic agents.

 

In the hunt for ErbB2's co-conspirators, Dr Muthuswamy's team focused on Brk, which they knew to be over-produced in many other types of cancer, including two-thirds of all breast cancers. A detailed analysis of changes that occurred in the genomes of a sample of breast cancer patients helped the group confirm that the expression of ErbB2 and Brk was directly linked.

 

By forcing the production of both ErbB2 and Brk within the same cell, they determined how Brk enhances ErbB2 activity and fortifies tumor cells against ErbB2-targeting drugs. “Our results might explain why the strategy of using ErbB2 inhibitors alone to treat breast cancers has fallen short,” added Dr Muthuswamy. “These findings may also suggest a way to treat patients with advanced ErbB2-positive tumors and those who've developed resistance to ErbB2 inhibitors – an idea that we're eager to test.”

 

According to the scientists, targeting Brk is a safe strategy because “Brk does not promote the proliferation of normal cells, and its expression in normal tissues is restricted to non-proliferating cells.” Inhibiting this protein might thus “produce fewer unwanted side effects than (targeting) other cancer-promoting proteins” which may be present in larger numbers.