Our application has broad implications for hematologic cancers but our specific focus will be on acute lymphoblastic leukemias. Evidence that monitoring minimal residual disease (MRD) has prognostic value is becoming increasingly strong, however the primary roadblock between deep clinical response and cure for many patients has been the inability to therapeutically target MRD. We are proposing to scale-up and validate a novel microfluidic system that monitors the mass of individual cells within an MRD sample with unprecedented precision before and after delivery of a particular treatment. The primary deliverable of this R33 application is a system that can be used in clinical studies to address the following question: Does the growth response of a patient's cancer cells obtained at the time of MRD to a particular therapy predict that therapy's efficacy for that patient? At present, cytotoxic therapy is simply intensified for patients with persistent MRD, rather than selectivity targeting it with a therapy known to be most effective for a particular patient. Our approach of assaying MRD for therapeutic sensitivity by a direct measure of cell growth would represent a significant advance in utilizing the presence of MRD in the treatment of leukemia.
Evidence that monitoring minimal residual disease (MRD) has prognostic value for acute lymphoblastic leukemias is becoming increasingly strong, however the primary roadblock between deep clinical response and cure for many patients has been the inability to therapeutically target MRD. We are proposing to scale-up and validate a novel microfluidic system that monitors the mass of individual MRD cells with unprecedented precision before and after delivery of a particular treatment. The primary deliverable of this R33 application is a system that can be used in clinical studies to address the following question: Does the growth response of a patient's cancer cells obtained at the time of MRD to a particular therapy predict that therapy's efficacy for that patient?
| Cetin, Arif E; Stevens, Mark M; Calistri, Nicholas L et al. (2017) Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation. Nat Commun 8:1613 |
| Stevens, Mark M; Maire, Cecile L; Chou, Nigel et al. (2016) Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate. Nat Biotechnol 34:1161-1167 |
| Cermak, Nathan; Olcum, Selim; Delgado, Francisco Feijó et al. (2016) High-throughput measurement of single-cell growth rates using serial microfluidic mass sensor arrays. Nat Biotechnol 34:1052-1059 |
