celecoxib + trastuzumab

Celecoxib + trastuzumab is a combination therapy consisting of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor classified as a nonsteroidal anti-inflammatory drug (NSAID), and trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2/ERBB2). This combination has been investigated primarily for the treatment of HER2-positive metastatic breast cancer, particularly in patients who have developed resistance to prior trastuzumab-based therapies. Celecoxib exerts antitumor effects by inhibiting COX-2 and modulating signaling pathways such as phosphoinositide-dependent kinase-1 (PDK-1)/Akt, which are implicated in tumor cell survival and proliferation. Trastuzumab binds to HER2 on cancer cells, blocking downstream signaling that promotes cell growth and survival. The rationale for combining these agents is based on preclinical evidence that concurrent inhibition of Akt signaling by celecoxib may enhance sensitivity to trastuzumab or overcome resistance mechanisms in HER2-positive breast cancer cells[1][3][2]. Clinical studies have evaluated this combination in women with metastatic breast cancer refractory to previous trastuzumab therapy[2].