Grant: Project Grant

Serine protease urokinase type plasminogen activator (uPA) and its receptor (uPAR) play an important role in tumor invasion, growth and metastasis. Targeting genes expressed by tumor cells is an attractive approach for early diagnosis and developing novel treatment strategies. Large-scale clinical studies in several cancers including those in breast and prostate cancer patients, have demonstrated increased expression of uPA-uPAR which play an important role in tumor growth and spread to different organs including skeleton which results in bone pain, nerve compression and immobility. In this proposal, using state-of-the-art models of cancer, we will elucidate the role of the uPAR and its different domains in tumor progression and metastasis to non-skeletal and skeletal sites. We will evaluate the role of uPAR in immune surveillance and determine the effects of inhibiting checkpoint protein inhibitors alone and in combination with anti-uPAR agents on tumor growth and metastasis. Using our highly selective lead anti-uPAR antibody, we will examine its efficacy alone and in combination settings to block cancer growth and spread to non-skeletal and skeletal sites using our mouse models of cancer. Collectively this research proposal will further clarify the role of the uPAR system in tumor growth and its spread to the skeleton. Results from these studies will play a key role in the optimization and clinical development of novel uPAR targeted therapeutic approaches alone and in combination setting against breast and prostate cancer growth and bone metastasis.