Professor of Oncology, Urology
Johns Hopkins Medical Institutions
Anti-cancer drug development; Normal and malignant stem cell biology
While there has been an explosion of knowledge about human carcinogenesis over the last 2 decades, unfortunately, this has not translated into the development of effective therapies for either preventing or treating the common human cancers. The goal of the Isaacs' lab is to change this situation by translating theory into therapy for solid malignancies, particularly Prostate cancer. Presently, a series of drugs discovered in the Isaacs' lab are undergoing clinical trials in patients with metastatic cancer. The ongoing drug discovery in the lab continues to focus upon developing agents to eliminate the cancer initiating stem cells within metastatic sites of cancer. To do this, a variety of bacterial and natural product toxins are being chemically modified to produce "prodrugs" whose cytotoxicity is selectively activated by proteases produced in high levels only by cancer cells or tumor associated blood vessel cells. In this way, these prodrugs can be given systemically to metastatic patients without un-acceptable toxicity to the host while being selectively activated to potent killing molecules within metastatic sites of cancer. Such a "Trojan Horse" approach is also being developed using allogeneic bone marrow derived Mesenchymal Stem cells which are genetically engineered to secrete "prodrugs" so that when they are infused into the patient, they selectively "home" to sites of cancers where the appropriate enzymatic activity is present to liberate the killing toxin sterilizing the cancer "neighborhood".