Grant: Operating Grant

Most cancer deaths are caused by spread of cancer cells from primary tumors to distant sites and subsequent formation of new tumors (cancer metastases). Cancers with metastatic spread are normally resistant to conventional chemotherapies and difficult to eradicate by radiotherapy. Moreover, aggressive doses are normally used in conventional treatments to achieve a greater therapeutic benefit, however at the price of more acute and long-term toxic side effects. Therefore novel treatment approaches are urgently needed. Recent studies have found that the same kind of protein exists on the newly formed blood vessels in tumors and on cancer cells. Targeting cancer drugs to this protein provides a promising therapeutic approach that can deprive nutrients of tumor and kill cancer cells that have high potential to metastasize. We have devised a novel nanoparticle drug carrier with about one-hundredth the diameter of a cancer cell that can effectively overcome drug resistance of breast cancer cells. We have demonstrated that co-administration of two cancer drugs that exhibit synergistic anticancer effect, by particulate carriers, significantly increases their anticancer efficacy in cells and in animals; and their co-nanoencapsulation enables the kill of drug resistant cancer cells at 30-fold lower doses than a conventional method. In this proposed research, we will develop nanoparticle carriers containing multiple synergistic cancer drugs with surface molecules specifically binding to tumor blood vessels and cancer cells. We will investigate the efficacy of these carriers in highly aggressive breast cancer cells and their primary and metastatic tumors grown in animal models. This innovative approach is expected to enhance the specificity and efficiency of cancer treatment while reducing the toxic side effects.