最近，肿瘤学最新技术发展在线资源网站“肿瘤学学习网络（Oncology Learning Network， https://www.oncnet.com/）”就本课题组提出的HER2阳性乳腺癌的治疗新策略采访了刘震教授，并刊登了题目为“Researcher Posit New Strategy for Treatment of HER2-Positive Breast Cancer”报道。
What existing data led you and your co-investigators to conduct this research?
To block the HER2 signaling pathway has been an effective strategy for the therapy of HER2 overexpressed breast cancer. Before my team conducted this research, the clinical treatment of early stage HER2+ breast cancer has mainly relied on monoclonal antibodies and tyrosine kinase inhibitors. Monoclonal antibody, such as pertuzumab, binds the extracellular sub-domain II of HER2 (a glycoprotein that belongs to the epidermal growth factor receptor (EGFR) family), blocking the dimerization of HER2 with other EGFR family members such as HER3 and then inhibiting the downstream signaling pathways. While tyrosine kinase inhibitors, such as, neratinib and lapatinib, bind the intracellular domain of HER2, suppressing the autophosphorylation of tyrosine and leading to growth inhibition of HER2+ cancer cells.
Please briefly describe your study and its findings. Were any of the outcomes particularly surprising?
We turned to a new strategy, using molecularly imprinted polymer nanoparticles (nanoMIP) that can bind HER2 through binding with its glycan chains, to prevent the dimerization. Our experiments indicated that the nanoMIP inhibited HER2+ cell proliferation at a 30% decrease and the mean tumor volume of nanoMIP-treated mice was only about a half of that of non-treated mice. Glycans are more accessible as compared with polypeptide domains of glycoproteins, but they are of very poor immunogenicity and their antibodies are rather limited. Because many types of cancerous cells overexpress certain glycoproteins at the cell surface, this new strategy opened a new access to not only the treatment of HER2+ breast cancer but also the treatment of other cancers.
What are the possible real-world applications of these findings in clinical practice?
Our nanoMIP is silica based, being highly biocompatible. Therefore, such nanoMIPs hold great potential in clinical cancer treatment. We are seeking collaborators for clinical investigations.
Do you and your co-investigators intend to expand upon this research? If so, what are/will be your next steps?
Yes, we are going to expand upon this research to a wide area which may be called nanoMIP-based cancer therapy. Our next goal is to develop a new method for the treatment of triple negative breast cancer, which is more challenging. Since to treat cancers by blocking specific signaling pathway with nanoMIPs is a general strategy, there are many possibilities that are worthy to explore.
Is there anything else pertaining to your research and findings that you would like to add?
In addition to MIP-based cancer therapy, we have developed a series of MIP-based fast disease diagnosis approaches.