AUA 2017: Highlights of Urologic Oncology Research

Boston, MA ( Dr. Aria Olumni gave the plenary audience an excellent and concise overview of the nanomedicine symposium presented earlier in the meeting. The first nanodrug to be approved by the FDA was Doxil in 1995. Doxil is doxorubicin encoated in a liposomal delivery platform. Ammonia released by tumor cells enters the liposome and forces release of the drug directly and only into the tumor microenvironment. Studies showed that because of its targeting capabilities, it had a dramatically improved toxicity profile compared to systemic treatment with doxorubicin.

More recently, there has been an explosion of techniques and innovative mechanisms for nanoparticle treatments.

Expansile nanoparticles describe a family of particles that can expand over 10-fold after delivery to the target tissue. For example, some take advantage of the lower pH within endosomes; once the nanoparticle is taken up by an endosome, it expands dramatically and is released into the target tissue. Other promising expansile nanoparticles are photoactive and can be targeted to expand in selected tissues by means of light photoactivation.

Spherical Nucleic Acids (SNAs) are an incredible advance in nanoengineering with nucleic acids. These SNAs are new and unnatural forms of DNA that have unique biologic activity that is completely different from linear DNA. SNAs utilize a spherical nanoparticle that can be tagged with bits of DNA. The advantages of these new nanoparticles are that they have minimal immune reactivity, they are resistant to nucleases, and have highly-selective targeting capabilities. Furthermore, they do not require transfection agents to effect cellular uptake.

Cell membrane-coated nanoparticle technology utilizes a novel mechanism to evade the immune system. For example, toxin nanosponges are polymers coated in a RBC membrane. These nanosponges, once in targeted tissue (including in blood, etc.), are released and then “soak up” and neutralize toxins. The early in-vivo studies of these nanosponges are very promising and may represent an exciting way to manage a wide variety of cancerous and noncancerous conditions in the near future.

More of us are familiar with circulating tumor cells (CTCs) and their utility in diagnostics and treatment personalization. However, there have been enormous recent advances in nanoengineering that led to the creation of the CTC-iChip by Mehmet Toner, PhD and colleagues. This CD-ROM like device performs a microfluidic depletion of hematopoietic cells to isolate untagged CTCs that can be collected for further use. Dr. Olumi presented an example of its use in a patient with metastatic CRPC whose CTCs revealed a variety of AR-variants. These diagnostic tools will ultimately be incorporated in algorithms to identify which treatment options will be the most effective for individual patients.

In conclusion, the synthesis of bioengineering, drug delivery, and informatics is the key to the future of nanomedicine. We are now perfectly situated to exploit the extraordinary advances in highly disparate fields that, when brought together, can produce miraculous new treatment options in the fight against cancer.

Presented By: Aria Olumi, MD, Massachusetts General Hospital

Written By: Shreyas Joshi, MD, Fox Chase Cancer Center
Twitter: @ssjoshimd

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA