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PRODUCED BY AND FOR MEMBERS OF THE DEPARTMENT OF SURGERY October 2016 | Archived Issues

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Surgery Grand Rounds

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Grand Rounds

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Education Schedule

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Education Schedule - October 2016 (PDF)  

Education Schedule - November 2016 (PDF)  


Surgery Scheduling

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Focusing on Triple-Negative Breast Cancer

Xiaogiang Cui, PhD

By Xiaojiang Cui, PhD

The team of Xiaogiang Cui, PhD, focuses on uncovering the biological basis and novel therapeutic targets for triple-negative breast cancer (TNBC) development and metastasis. The team is also exploring regenerative tissue engineering of the human mammary gland.

TNBC is one of the most aggressive types of breast cancer and has the highest mortality rate among all breast cancer subgroups. It is generally diagnosed based upon the absence of three "receptors" known to fuel most breast cancers — estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2. These tumors generally do not respond to common receptor-targeted treatments. Unlike other breast cancer types, it frequently metastasizes to the brain, the most feared complication of systematic cancer.

Currently, the only systemic treatment option for these breast cancers is chemotherapy. The development of effective targeted therapies for this devastating disease depends on our elucidation of its molecular and genetic mechanism.

The team, in collaboration with clinicians at the Cedars-Sinai Saul and Joyce Brandman Breast Center - A Project of Women's Guild, is pursuing several innovative research projects in this direction. One such project examines the FOXC1 gene, identified by gene expression profiling of human breast tumors as a critical biomarker for TNBC. Team members revealed that the FOXC1 gene controls TNBC cell growth and invasion and that its expression levels predict brain metastasis in human breast cancer. The group is testing whether FOXC1 regulates the seeding and growth of breast cancer cells in the brain.

Another project is related to therapy resistance in breast cancer treatment targeting cancer stem cells. Hedgehog (Hh) proteins are key regulators of cancer stem cells and are considered promising targets for cancer treatment. But results of ongoing clinical trials show anti-Hh drug resistance is common.

These drugs target an Hh-interacting protein called SMO, which transmits Hh signals to gene expression and cell function changes. Cui's group revealed that FOXC1 can activate the genes, normally activated by Hh and SMO, in an Hh/SMO-independent manner, thereby inducing resistance to anti-Hh drugs in breast cancer cells. This work demonstrates a novel resistance mechanism for anti-Hh drugs in cancer cells and allows for designing strategies to more effectively kill cancer stem cells in cancer treatment.

Xiaojiang Cui, PhD, is associate professor in the Department of Surgery and research scientist in the Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute.