Pilot Project 4

Single-Cell Deep-Profiling of Signaling and Genomic Alterations Mediating the Evolution of Chemo-Therapeutic Resistance in Breast Cancer

Project Investigators: Ben Cosgrove

Additional Collaborators: Olivier Elemento, (Weill Cornell Medicine)

Breast cancer manifests as a genomically and phenotypically diverse disease even in individual patients, complicating chemo-therapeutic efficacy. We will develop integrated deep-profiling approaches employing single-cell genomic sequencing and mass cytometry to identify stem-cell-like subpopulations of breast cancer cells that are resistant to chemotherapeutic treatment. In particular, we aim to dissect the subpopulations of triple-negative (ERPRERBB2) breast cancer cells that are resistant to targeted dual inhibitior of the phosphatidylinositol-3 kinase (PI3K) pathway and the enzyme poly-ADP ribose polymerase (PARP), and reconstruct the genomic alterations and signaling-network profiles associated with their resistant phenotypes. We will use this approach to develop adaptive combinatorial treatment strategies to ameliorate clonal evolution of chemotherapeutic resistance in vitro and, in future work, in patient-derived xenograft models.