Scientists Identify Potential Therapeutic Target for Treatment-resistant Breast Cancer

by Rajashri on Sep 24 2008 3:07 PM

A potential therapeutic target for the treatment resistant breast cancer has been identified by researchers from Wyeth's Department of Discovery Translational Medicine.

The researchers have revealed that the activation of Src signalling pathway might make breast cancer resistant to treatment.

The team suggested that inhibiting Src signalling while giving standard medical treatment could help overcome the resistance.

"If this finding is confirmed in clinical trials, which are currently being designed, then inhibiting Src signaling while giving standard of care medical treatment might allow us to overcome some aspects of drug resistance in the clinic," said Christina M. Coughlin, M.D., Ph.D., medical director and global medical monitor at Wyeth Pharmaceuticals, who lead this research in Wyeth's Department of Discovery Translational Medicine.

The identification of genetically altered pathways in human tumours, and their subsequent inhibition, has become a major treatment strategy in many cancers.

Coughlin said researchers suspected that some part of its pathway, either downstream or upstream, might be driving tumour development and treatment resistance.

During the study, the researchers performed quantitative tissue microarray sampling among almost 650 patient samples to analyze for the expression of markers of the Src pathway.

They identified subsets of patients with high Src activation who expressed low levels of estrogen receptor, progesterone receptor and HER2, also known as triple negative breast cancer, as well as subsets expressing the estrogen or progesterone receptors.

These patient sets had lower overall survival associated with expression of Src signalling pathway biomarkers, which suggests that Src pathway activation may have played a role in treatment resistance.

"This gives us all the pieces to the puzzle. This type of cancer signalling pathway study holds the potential to help determine who the appropriate patients are for the newer targeted drugs that we have to treat breast cancer in the absence of genetic signals for a given drug target," Coughlin said.

"We can then translate that information into molecular diagnostics that can be applied within the clinical trials," she added.

The data was presented at the American Association for Cancer Research Molecular Diagnostics in Cancer Therapeutic Development meeting.