Knock down of Cxcr2 Enhances Sensitivity to Chemotherapy

Cancer has always had and still has a huge impact on human society. According to the American Cancer Society, cancer accounts for nearly one quarter of deaths in United States, exceeded only by heart disease. In 2006, there were 559,888 cancer deaths in the US. According to the World Health Organization, deaths from cancer worldwide are projected to continue rising, with an estimated 12 million deaths in 2030. Although prostate cancer is the most prevalent cancer among males, breast cancer is the most prevalent cancer among females. The current cancer therapy, which is also known as the conventional cancer therapy, mainly consists of either chemotherapy, surgery or radiation therapy. A lot of times these therapies are successful in treating the disease but many times they fail to do so, which leads to the recurrence and progression of the disease. Chemotherapy and radiation therapy have side effects on the human body, which leads to toxicity. As opposed to early stage disease, many challenges exist in the current management of advanced stage breast cancer as there are fewer recognized therapeutic strategies, often due to therapy resistance. The major challenges right now in this field of research are to improve the efficacy of the current therapeutic regimens by limiting its toxicity and the reversal of therapy resistance i.e. to make tumor cells more sensitive to therapy. Recent reports suggest that malignant cells that survive initial chemo-and radiation therapy often express inflammatory cytokines such as CXCR2 ligands, which provides survival benefit making tumors resistant. The specific objective of this study is to develop strategy to manipulate chemokine-chemokine receptor network to develop effective therapy with limited toxicity for drug-resistant breast cancer. CXCR2 and its ligands like CXCL1, 3, 5 and 8 have been shown to play an important role in inflammation and tumor progression. They have been shown to be associated with the aggressiveness of the tumor cell lines. CXCR2 ligands enhance malignant cell proliferation and survival. There is an increase in the levels of CXCR2 ligands in the patient's body in response to chemotherapy. When the tumor cells are exposed to chemotherapy drugs, there is an increase in the production of CXCR2 ligands, which bind to CXCR2 leading to therapy resistance. Based on these previous studies, we hypothesize that inhibition of CXCR2 and its ligands signaling can enhance the efficacy of chemotherapeutic agents in malignant breast cancer. The specific objective of this study is …