Inhibiting breast cancer by targeting the thromboxane A2 pathway

Targeting the estrogen receptor as a strategy has been the gold standard for breast cancer chemoprevention or breast cancer recurrence, but its benefit is limited to estrogen receptor-positive tumors. Cyclooxygenases have been implicated in mammary tumorigenesis. We sought to identify the key prostaglandin responsible for the pro-neoplastic effect of cyclooxygenases and develop prostaglandin-targeted strategies for breast cancer chemoprevention or therapy. Immunohistochemical analysis revealed that either thromboxane A 2 synthase 1 or the thromboxane A 2 receptor is highly expressed in human breast tumors as well as premalignant lesions, but not in normal mammary tissues. Clinically, the thromboxane A 2 pathway might be associated with HER2-positive and axillary lymph node metastasis in human breast cancer. We found that the thromboxane A 2 pathway was required for breast cancer cell growth, anchorage-independent growth and invasion capabilities. Importantly, we discovered that switching off thromboxane A 2 biosynthesis effectively suppressed either MMTV-HER2-driven mammary tumorigenesis or breast cancer metastasis in preclinical animal models. Taken together, this study established a critical pathophysiological role of the thromboxane A 2 pathway in breast cancer, and provided a rationale for introducing a strategy targeting thromboxane A 2 for breast cancer chemoprevention and therapy. Breast cancer: Pathway target identified The identification of a signaling pathway connected to the progression of breast cancer could prove a valuable therapeutic target. The breast cancer treatment tamoxifen, although successful, is limited to certain tumor types, and so the search is on to pinpoint molecular targets that are ubiquitous across breast cancers. Zigang Dong at the University of Minnesota, US, and co-workers identified that the thromboxane A 2 (TXA 2 ) pathway is highly-expressed in human breast tumors and premalignant lesions. Further examination showed that TXA 2 is crucial for tumor cell growth and metastasis. When the researchers knocked-out TXA 2 production in mouse models, this suppressed both the formation and spread of tumors. The team advise caution because TXA 2 is also required for wound healing and other key processes, although short-term bursts of pathway suppression may be an option for breast cancer therapy.