ArticleCancer cell international2020
Exploiting collateral sensitivity controls growth of mixed culture of sensitive and resistant cells and decreases selection for resistant cells in a cell line model.
Article in Cancer cell international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- A novel combination therapy for ER+ breast cancer suppresses drug resistance via an evolutionary double-bind.Molecular systems biology · 2026Article
- System analysis links SMARCD3 regulons to growth signaling and MEK inhibitor response in everolimus-resistant ER+ breast cancer cells.Cell reports. Medicine · 2025Article
- Cellular interactions within the immune microenvironment underpins resistance to cell cycle inhibition in breast cancers.Nature communications · 2025Article
- Methylstat sensitizes ovarian cancer cells to PARP-inhibition by targeting the histone demethylases JMJD1B/C.Cancer gene therapy · 2025Article
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- ONC201/TIC10 enhances durability of mTOR inhibitor everolimus in metastatic ER+ breast cancer.eLife · 2023Article
- Phylogenetic inference from single-cell RNA-seq data.Scientific reports · 2023Article
- Establishment and Molecular Characterization of an In Vitro Model for PARPi-Resistant Ovarian Cancer.Cancers · 2023Article
- Cell facilitation promotes growth and survival under drug pressure in breast cancer.Nature communications · 2023Article
- Dynamic Phenotypic Switching and Group Behavior Help Non-Small Cell Lung Cancer Cells Evade Chemotherapy.Biomolecules · 2021Article
- Targeting WEE1 Inhibits Growth of Breast Cancer Cells That Are Resistant to Endocrine Therapy and CDK4/6 Inhibitors.Frontiers in oncology · 2021Article
- Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Frontiers in oncology · 2021Review
- Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer.PloS one · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCDK4/6 inhibitors such as ribociclib are becoming widely used targeted therapies in hormone-receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. However, cancers can advance due to drug resistance, a problem in which tumor heterogeneity and evolution are key features.
methodsRibociclib-resistant HR+/HER2- CAMA-1 breast cancer cells were generated through long-term ribociclib treatment. Characterization of sensitive and resistant cells were performed using RNA sequencing and whole exome sequencing. Lentiviral labeling with different fluorescent proteins enabled us to track the proliferation of sensitive and resistant cells under different treatments in a heterogeneous, 3D spheroid coculture system using imaging microscopy and flow cytometry.
resultsTranscriptional profiling of sensitive and resistant cells revealed the downregulation of the G2/M checkpoint in the resistant cells. Exploiting this acquired vulnerability; resistant cells exhibited collateral sensitivity for the Wee-1 inhibitor, adavosertib (AZD1775). The combination of ribociclib and adavosertib achieved additional antiproliferative effect exclusively in the cocultures compared to monocultures, while decreasing the selection for resistant cells.
conclusionsOur results suggest that optimal antiproliferative effects in heterogeneous cancers can be achieved via an integrative therapeutic approach targeting sensitive and resistant cancer cell populations within a tumor, respectively.
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