Development of novel therapies for urological malignancies

Bladder cancer:
The bladder cancer research laboratory is incorporated in the clinical department, providing a closely integrated team with clinical care, research and clinical trials expertise. Besides providing regional expertise in the management of non-muscle invasive bladder cancer using intravesical BCG therapy, the team performs translational research on new diagnostic tools and treatments.

Bladder cancer patients do not all respond well to the standard BCG immunotherapy. BCG failures are more likely to have disease progression. Therefore, our team is engaged in developing novel therapies for bladder cancer using an orthotopic murine model of bladder cancer. This comprises the development of novel immunotherapeutic agents (such as Lactobacillus rhamnosus GG and extracellular vesicles); identification of the cause of poor response to BCG immunotherapy (eg. single nucleotide polymorphisms and methylation), improving the response using combination therapeutics (clinical trials with Vitamin D and BCG); and the improvement of response to chemotherapeutic drugs using nanoparticles. The latter projects were performed in collaboration with the Departments of Biomedical Engineering, Chemical and Biomolecular Engineering and Electrical and Computer Engineering, and the Institute of Health Innovation and Technology in NUS. Nanocarriers with the ability to package cytotoxic drugs and with targeting properties to ensure delivery to tumors have shown promising results in mice. Development of a miniaturized implantable wirelessly powered light-emitting diode as a light source for photodynamic chemotherapy using glycosylated nanocarriers carrying chlorin e6 and gemcitabine elaidate greatly reduced the tumor burden in mice with orthotopic bladder cancer and reduced the need for expensive devices for photodynamic therapy.

Figure. Wireless microLED for treating orthotopic bladder tumors. A) Device implantation and schematic of the structure of the device and B) experimental schedule and tumor size as measured by PSA secretion in ruin ear day 25 and final tumor burden in groups treated with glycosylated nanocarrier with Ce6 and gemcitabine (50GCG) and 50GCG and PDT compared to control mice.
Papers of interest:
Adv Sci (Weinh). 2022 May;9(16):e2200731. doi: 10.1002/advs.202200731. Sun B, Rahmat JN, Kim HJ, Mahendran R, Esuvaranathan K, Chiong E, Ho JS, Neoh KG, Zhang Y. Wirelessly Activated Nanotherapeutics for In Vivo Programmable Photodynamic-Chemotherapy of Orthotopic Bladder Cancer.
Nanomedicine. 2022 Nov;46:102600. doi: 10.1016/j.nano.2022.102600. Mullapudi SS, Rahmat JN, Mahendran R, Lim YK, Ong LT, Wong KY, Chiong E, Kang ET, Neoh KG. Tumor-targeting albumin nanoparticles as an efficacious drug delivery system and potential diagnostic tool in non-muscle-invasive bladder cancer therapy.
Biomedicines. 2021 Nov 25;9(12):1766. doi:10.3390/biomedicines9121766. Tham SM, Rahmat JN, Chiong E, Wu Q, Esuvaranathan K, Mahendran R. Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with GMCSF+IFN α  Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model.

Prostate cancer:

We are a regional leader in the clinical management of prostate cancer. NUH Urology department has participated in landmark trials such as PROSPER and PREVAIL for castrate-resistant metastatic prostate cancer and is at the forefront of advancing clinical practice in therapy and diagnostics for prostate cancer. The assessment of abiraterone dose reduction and response in a Phase I clinical trial for patients with advanced prostate cancer is ongoing as well as the development of nanogels to improve prostate cancer therapy. For diagnostics, improving biopsies or verifying less invasive methods of detection (such as liquid biopsy) are among the studies conducted.