Despite the improvement of medical study, new cases in colorectal cancer increased along the years. Monoclonal antibodies such as cetuximab are applied in clinical therapy. These monoclonal antibodies target EGFR and then indirectly inhibit downstream RAS/RAF-mediated cell proliferation and metastasis signaling pathways. However, 30-50% of colorectal cancer tumors contain KRAS mutation which resulted in no response towards EGFR inhibitors. Therefore, novel treatment and target for treating KRAS mutated colorectal cancer is needed. RAF kinase inhibitors, which target RAS/RAF, are therefore studied intensively. Carbon nanomaterials (CNMs) (including carbon nanotubes and graphene quantum dots) have attracted an increasing amount of interest because of its potential applications in biomedical fields such as biological imaging and drug control-release, which provides more therapeutics possibilities for future cancer treatments. Moreover, they can be functionalized to be attached with specific drugs, antibodies or fluorescent molecules and therefore CNMs are high potential candidate materials in drug delivery. The aim of this study is to develop CNMs as multifunctional drug delivery system, to inhibit KRAS mutated colorectal cancer cells and tumors in xenograft experiment. We will conjugate polyethylene glycol (PEG) and folic acid (FA) to CNMs, which improves dispersion of CNMs in solution and increases the biocompatibility of CNMs. Our preliminary data are promising. Next, we would modify EGFR monoclonal antibody and RAF kinase inhibitor onto CNMs to greatly improve their ability of targeting and killing of colorectal cancer cells. We expect that this project will result in a better understanding of the colorectal cancer cell inhibition caused by multifunctional drug delivery system, and set up a novel multifunctional drug delivery system which could benefit the future treatment in KRAS mutated colorectal cancer.
|Effective start/end date||8/1/16 → 7/31/17|
- Carbon nanomaterials
- KRAS mutation
- RAF kinase inhibitor
- colorectal cancer
- drug delivery system
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