As our population aging, prostate cancer (PCa), a typical androgen-dependent cancer, has become the most common malignancy diagnosed in U.S. males. Bone is the major distant metastatic site for PCa. Mortality of PCa patients as the second to that of lung cancer is due to the emergence of castration resistant PCa (CRPC) from metastatic site. It is postulated that emergence of CRPC cells derive from the stem cell population in prostate gland after malignant transformation. However, no effective regimens are currently available because the biology of CRPC is not well characterized. We are currently characterizing the phenotype of normal stem cell population particularly molecular defect(s) of homeostatic machinery in those cells that can lead to PCa progression, in particular, the outgrowth of CRPC cells with various phenotypes such as androgen receptor variant or neuroendocrine. In addition, we are designing these nanoparticles as a cancer specific drug delivery system with molecular imaging capability. Our goal is to develop the concept of targeted theranostics in which agent has a dual function as therapeutics and imaging.
The incidence of renal cell cancer (RCC) has been steadily rising by 2–4% each year. RCC is by far the most lethal urologic malignancy once it becomes metastatic. The median overall survival of un-treated metastatic disease is 5 months with 1-year survival of only 29%. RCC commonly metastases to lung, bone, liver, lymph nodes and the brain; the prognosis is known to vary with the involved target organ, bone and brain involvement resulting in adverse survival compared to lung and lymph nodal disease. Advanced metastatic RCC (mRCC) is highly resistant to radiation therapy (RT) and chemotherapy because cancer cells can obtain mesenchymal phenotype that may contribute to invasion and metastasis through epithelial-to-mesenchymal transition (EMT) that increases the ability of cancer cells to cross endothelial barriers and enter blood and lymphatic circulations. Clinically, the presence of a sarcomatoid component is often found in metastatic lesion of RCC and associated with high mortality. Currently, we are determining master molecular driver underlying RCC metastasis with therapeutic resistant phenotypes. In addition, we are identifying potential prognostic biomarker(s), particularly, in tumor-derived exosomes that can be developed into clinical applicable liquid biopsy detection.
The majorities of transitional cell carcinoma (TCC) of the bladder are superficial and have a high rate of recurrence following transurethral resection (i.e., TURP). Currently, TCC is the second most common malignancy of all genitourinary cancers and the second leading cause of death from cancer of the urinary tract. TCC often recurs recurrence and becomes invasive and metastatic after TURP, which leads to the mortality eventually. Current regimens such as chemotherapy are not targeting cancer specifically often associated with significant side effect. The current research in my laboratory is to develop gene therapy specific to TCC.