Identifying States of Collateral Sensitivity during the Evolution of Therapeutic Resistance in Ewing's Sarcoma
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Abstract
Advances in the treatment of Ewing's sarcoma (EWS) are desperately needed, particularly in the case of metastatic disease. A deeper understanding of collateral sensitivity, where the evolution of therapeutic resistance to one drug aligns with sensitivity to another drug, may improve our ability to effectively target this disease. For the first time in a solid tumor, we produced a temporal collateral sensitivity map that demonstrates the evolution of collateral sensitivity and resistance in EWS. We found that the evolution of collateral resistance was predictable with some drugs but had significant variation in response to other drugs. Using this map of temporal collateral sensitivity in EWS, we can see that the path toward collateral sensitivity is not always repeatable, nor is there always a clear trajectory toward resistance or sensitivity. Identifying transcriptomic changes that accompany these states of transient collateral sensitivity could improve treatment planning for patients with EWS.
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A variety of evolutionary trajectories can lead to the same phenotype.
“As seen in experimental and natural evolution, a variety of evolutionary trajectories can lead to the same phenotype11–14.”
From Exploiting convergent phenotypes to derive a pan-cancer cisplatin response gene expression signature (2023) · cites this paper as [12]
The Results (‘Surveying the Stochasticity of Evolution’; page unavailable) report that experimental replicates consistently acquired resistance to some drugs while diverging in their responses to others. This is consistent with different evolutionary outcomes accompanying a shared resistance phenotype, but the paper does not establish that distinct trajectories produced that same phenotype in natural evolution. (LLM, conf=0.78)
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Cites
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Cited by
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Exploiting convergent phenotypes to derive a pan-cancer cisplatin response gene expression signature
Scarborough, J. A., Eschrich, S. A., Torres-Roca, J., Dhawan, A., & Scott, J. G. (2023) · npj Precision Oncology · doi:10.1038/s41698-023-00375-y · Cited by 14 · see citing works
Self-citation
- Authors
- Scarborough, J. A., McClure, E., Anderson, P., Dhawan, A., Durmaz, A., Lessnick, S. L., Hitomi, M., & Scott, J. G.
- Affiliations
- Cleveland Clinic (US)
- Nationwide Children's Hospital (US)
- Corresponding author
- Scott, Jacob G.
- ORCID
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 23
- Issue
- 7
- Pages
- 101293
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC7334607
- OpenAlex
- W3036606715
- Cited by
- 38
- References
- 1
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 12 · 2023: 6 · 2022: 9 · 2021: 3 · 2020: 1
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (T32GM007250, K12CA076917)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- Ewing sarcoma, collateral sensitivity, treatment resistance, drug resistance evolution, metastatic sarcoma, transcriptomic changes, treatment planning
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