Grant: Strategic Projects - Group

Metastases are secondary tumors that originate from a malignant primary tumor and invade different organs; the cells in primary and secondary tumors are similar for many cancers. Pathologists can predict the ability of a primary tumor to metastasize by microscopic examination of a tumor biopsy; however, such examination does not help to objectively detect metastases. The difficulty of detecting and eradicating metastases significantly contributes to cancer mortality. Indeed, with limited factual information on metastases existence, the therapy is applied blindly and often fails because of the lack of objective means of assessing its effectiveness. Importantly, a therapy that is efficient for one patient often does not work for another. Cancer therapy could be dramatically improved if a technology for personalized diagnosis of metastatic cancers and monitoring their response to therapy were available. Here we propose such a technology - Aptamer-based Metastases Detection (AptaMeD). Aptamers are short DNA strands capable of selectively binding their targets, e.g. molecules on the cell surface. The idea of AptaMeD originates from our insight, that due to the common nature of primary and secondary tumors, DNA aptamers that selectively bind primary-tumor cells would also selectively bind secondary-tumor cells. They could, therefore, serve as tracers of metastases. AptaMeD involves the following conceptual steps: (i) biopsies from the primary tumor and normal tissues are used to generate Aptamer Complement of Cancer-Unique Molecules (ACCUM) that binds cancerous, but not normal cells, (ii) ACCUM is protected from degradation and body clearance and labelled for detection, (iii) ACCUM is introduced into the patient and allowed to accumulate in metastases, and (iv) whole-body imaging is used to detect the label in the metastases. AptaMeD will allow for the monitoring of the metastases' response to the therapy. Advantageously, the tumor-specific aptamers can be potentially used as vehicles for delivery of drugs to the metastases. Libraries of aptamers will be collected over time and can eventually simplify metastases detection. In addition to its potential clinical applications, AptaMeD promises to be an indispensable research tool.