Summary of Federal Project Grant Award

The National Cancer Institute awarded the University of Pittsburgh $408,829 on June 12, 2026, under the Cancer Detection and Diagnosis Research Program (CFDA 93.394) to develop advanced methodologies for identifying and targeting polyploid giant cancer cells (PGCCs) as a strategy to overcome treatment resistance in breast cancer. The project, which runs through May 31, 2028, focuses on enhancing a high-throughput single-cell morphological analysis pipeline capable of quantifying PGCCs and screening compounds for efficacy. Leveraging preliminary work that successfully screened 2,726 compounds, the research team will improve the robustness and accuracy of their detection system across diverse laboratory conditions and staining/imaging protocols, utilizing deep learning algorithms to accelerate the discovery of therapeutic strategies targeting PGCCs. This work addresses a critical gap in current screening methods, as traditional assays and detection approaches lack the sensitivity and throughput necessary for identifying small populations of PGCCs that contribute to disease relapse and therapeutic resistance.

In addition to the screening pipeline development, the project incorporates single-cell RNA sequencing (scRNA-seq) analysis to characterize altered gene expression patterns in PGCCs, with particular focus on FOXM1, a transcription factor linked to poor cancer outcomes and cell cycle regulation, and ferroptosis-related pathways. The research aims to establish a robust, multi-laboratory platform suitable for widespread adoption in PGCC and whole-genome doubling studies, thereby enabling the biomedical research community to identify novel therapeutic targets and compounds that specifically overcome the enhanced therapeutic resistance exhibited by polyploid cancer cells.