Studying why some breast cancer patients are Herceptin-resistant

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Xuguang
PhD student Xuguang Liu

Greetings! I’m Xuguang Liu, a fourth-year PhD student in the Biochemistry Department at Western University. My current research project is focused on the development of Herceptin resistance in HER2-positive breast cancer. Particularly, we’re trying to establish a diagnostic technique that might be able to further classify this cancer type.

HER2-positive breast cancer is diagnosed as over-activity of the HER2 gene. Two target therapeutics, Tykerb and Herceptin, have been clinically approved and both are designed to reduce HER2 activity.

A common problem for the target therapeutics is drug resistance. For instance, only 30 per cent of patients diagnosed as HER2-positive respond to Herceptin in the beginning, which is defined as “intrinsic resistance.” In this 30 per cent of patients, many develop “acquired resistance” as soon as several months after treatment. The mechanism of resistance is complicated, but it’s well accepted that many HER2-like players can be over-activated during treatment, which in turn compensate for the loss of HER2 activity.

We’re trying to establish a strategy to define the activation status of all these players from a single test on a biopsy sample. In a preliminary test, we’ve successfully isolated the activity-deciding fragments of these players from a tiny amount of lab-cultured cells, and made them analyzable in the mass-spectrometry instrument.

Future work will aim to establish a standard operating procedure in biopsy-sample diagnosis. Finding these co-players will facilitate a further classification of HER2-positive breast cancer and the design of precision treatment for each breast cancer patient.

Thank you to BCSC for your trainee support!
 – Xuguang Liu, PhD Student
Pamela Greenaway-Kohlmeier Translational Breast Cancer Research Unit, London Health Sciences Centre

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