Injectable thermogelling cisplatin-loaded hydrogels for combined chemo-radiation therapy in cervical cancer
Mentor: Robert A. Cormack, PhD (Dana Farber Cancer Institute)
The effectiveness of Radiation Therapy is limited by the amount of radiation that can be delivered before severely damaging the surrounding tissue. To combat the potential short and long term toxicity issues associated with radiation therapy, my project will further current cervical cancer brachytherapy research by combining it with chemotherapy. We hypothesize that a combined chemo-radiation therapy approach will not only improve the therapeutic efficacy but also decrease the radiation associated toxicities. Current brachytherapy practices utilize polymeric implants known as ‘spacers’ in between the two radioactive seeds. The sole purpose of this practice is to provide a uniform dose distribution in a tumor. However, preliminary collaborative studies between Northeastern University and Brigham and Women’s Hospital, have shown that these spacers can be modified with chemotherapeutic drugs, which can improve chemo-radiation therapy. In collaboration with my mentor Dr. Robert Cormack, we propose that the use of a injectable thermogelling hydrogel polymer (poly (N-isopropyl acrylamide)-based) doped with chemotherapeutic drug, Cisplatin, will provide a fast and sustained drug release profile allowing for radio sensitization and better radiation therapy. We plan to investigate the effectiveness of the hydrogel-based polymer composite to radiosensitive tumor cells and provide better therapeutic efficacy while lowering radiation doses and minimizing toxicities in cervical cancer.
The chemotherapy drug cisplatin is a front-line therapy in the treatment of cervical cancer. Cisplatin’s basic mechanism works because it creates inter- and intra- strand crosslinks in the DNA. As a result, inhibition of gene transcription and DNA replication by DNA cross-linking blocks protein synthesis and cell multiplication. This image gives someone who is not familiar with the cisplatin mechanism a basic understanding of how cisplatin works and affects the cell. Source: Wilson, George D. "Radiation and the Cell Cycle, Revisited." Cancer Metastasis Rev Cancer and Metastasis Reviews 23.3/4 (2004): 209-25. Research Gate. Web. 2 Feb. 2016. Source: