Journal
SCIENCE ADVANCES
Volume 8, Issue 8, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abm1831
Keywords
-
Categories
Funding
- European Union [667403, 965193]
- Academy of Finland [344697, 325956, 289059, 322927, 294023, 319243]
- Sigrid Juselius Foundation
- Cancer Foundation Finland
- Academy of Finland (AKA) [325956, 322927, 294023, 289059, 344697, 319243, 322927, 325956, 319243, 289059, 294023] Funding Source: Academy of Finland (AKA)
Ask authors/readers for more resources
Chemotherapy resistance is a major contributor to cancer mortality, and a study focusing on high-grade serous ovarian cancer found that a stress-associated cell state consistently increased during chemotherapy, which was associated with poor progression-free survival.
Chemotherapy resistance is a critical contributor to cancer mortality and thus an urgent unmet challenge in oncology. To characterize chemotherapy resistance processes in high-grade serous ovarian cancer, we prospectively collected tissue samples before and after chemotherapy and analyzed their transcriptomic profiles at a single-cell resolution. After removing patient-specific signals by a novel analysis approach, PRIMUS, we found a consistent increase in stress-associated cell state during chemotherapy, which was validated by RNA in situ hybridization and bulk RNA sequencing. The stress-associated state exists before chemotherapy, is subclonally enriched during the treatment, and associates with poor progression-free survival. Co-occurrence with an inflammatory cancer-associated fibroblast subtype in tumors implies that chemotherapy is associated with stress response in both cancer cells and stroma, driving a paracrine feed-forward loop. In summary, we have found a resistant state that integrates stromal signaling and subclonal evolution and offers targets to overcome chemotherapy resistance.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available