Platform for the enrichment of circulating tumor cells (CTCs) for characterization and sensitivity to anti-cancer drugs

Challenge: A major challenge in cancer therapy is to stop cancer cells before they metastasize to other tissues, at which point the disease may become resistant to therapeutic intervention. During cancer progression, circulating tumor cells (CTCs) are shed from the primary tumor or its metastatic sites and their number follow closely the progression of the disease. However, CTCs are heterogenous and circulate in very low numbers making it difficult to isolate and study them using standard blood testing procedures.

Solution: To overcome this limitation, the team has used a method called aphaeresis to isolate, characterize and expand CTC subpopulations from the blood of triple negative breast cancer patients. Using negative selection (eliminating normal cells bearing a panel of surface markers), the researchers isolated and cultured CTCs in high enough numbers to be characterized, stored for later use, and used for drug sensitivity assays. This methodology is an improvement of several orders of magnitude compared to current isolation methodologies. The team also used RNA single-cell analysis to further characterize the heterogeneity of the CTC population.

Achievements/Impact: The team has developed a reliable technological platform for isolation, characterization and in vitro testing of CTCs in large quantities from cancer patients. Since these CTCs can now be cultured in vitro, their sensitivity or resistance to chemotherapeutic agents such as tamoxifen, herceptin, taxol or doxorubicin can be evaluated. The team indeed demonstrated that the sensitivity of CTCs isolated from specific breast cancer patients treated with these chemotherapeutic agents correlated well with the patient’s response. The platform developed during this project is not limited to breast cancer but will be readily applicable to other types of cancers including prostate, lungs, and melanoma.