Therapy-Tolerant Persister Cells and Developmental Reprogramming in KRAS-Mutant Cancer
Session Number
3
Advisor(s)
Dr. Nitu Kumari, Dr. Yogesh Goyal, Northwestern University
Location
A151
Discipline
Medical and Health Sciences
Start Date
15-4-2026 2:15 PM
End Date
15-4-2026 3:00 PM
Abstract
Acquired resistance to cancer therapy remains a critical clinical obstacle. In KRAS-mutant cancers - representing ~25% of human malignancies—targeted inhibitors such as sotorasib achieve initial responses, but median progression-free survival is only 6.3 months. Similarly, gemcitabine, the backbone of pancreatic cancer treatment, frequently fails within weeks. A unifying mechanism across these failures is the emergence of drug-tolerant persister (DTP) cells: small subpopulations that enter reversible, quiescent states upon drug exposure, evade therapy, and drive recurrence. This project investigates whether therapy-resistant cancer cells adopt developmental-like transcriptional programs, including embryonic diapause, epithelial-mesenchymal plasticity, and reactivated Hedgehog/Wnt/Notch signaling, as a generalizable survival strategy. Using multi-modal datasets from public repositories and the Goyal Lab at Northwestern University, we compare cellular responses to chemotherapy (gemcitabine) and targeted therapy (sotorasib) in KRAS-mutant cancers. This term establishes foundational infrastructure: a comprehensive literature synthesis, systematic curation and annotation of RNA-seq and imaging datasets, and initial computational analyses of therapeutic response trajectories. Results will be presented. By identifying conserved resistance signatures across cytotoxic and targeted therapies, this work aims to enable predictive biomarker development and guide adaptive treatment strategies for patients with KRAS-mutant malignancies.
Therapy-Tolerant Persister Cells and Developmental Reprogramming in KRAS-Mutant Cancer
A151
Acquired resistance to cancer therapy remains a critical clinical obstacle. In KRAS-mutant cancers - representing ~25% of human malignancies—targeted inhibitors such as sotorasib achieve initial responses, but median progression-free survival is only 6.3 months. Similarly, gemcitabine, the backbone of pancreatic cancer treatment, frequently fails within weeks. A unifying mechanism across these failures is the emergence of drug-tolerant persister (DTP) cells: small subpopulations that enter reversible, quiescent states upon drug exposure, evade therapy, and drive recurrence. This project investigates whether therapy-resistant cancer cells adopt developmental-like transcriptional programs, including embryonic diapause, epithelial-mesenchymal plasticity, and reactivated Hedgehog/Wnt/Notch signaling, as a generalizable survival strategy. Using multi-modal datasets from public repositories and the Goyal Lab at Northwestern University, we compare cellular responses to chemotherapy (gemcitabine) and targeted therapy (sotorasib) in KRAS-mutant cancers. This term establishes foundational infrastructure: a comprehensive literature synthesis, systematic curation and annotation of RNA-seq and imaging datasets, and initial computational analyses of therapeutic response trajectories. Results will be presented. By identifying conserved resistance signatures across cytotoxic and targeted therapies, this work aims to enable predictive biomarker development and guide adaptive treatment strategies for patients with KRAS-mutant malignancies.