---
title: "Dose Fluctuations in Cancer Therapy: Balancing Tumor Control and Resistance"
id: "pubmed-42682083"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42682083"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42682083/"
doi: "10.1158/0008-5472.CAN-26-2187"
published_at: "2026-09-02T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Dose Fluctuations in Cancer Therapy: Balancing Tumor Control and Resistance
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42682083
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42682083/)
- **DOI:** [10.1158/0008-5472.CAN-26-2187](https://doi.org/10.1158%2F0008-5472.CAN-26-2187)
- **Published At:** 2026-09-02T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The commentary reviews how cancer treatment outcomes depend on **dose**, treatment schedule, and a proposed third dimension: deliberate **dose fluctuations**. - West et al. tested variable dosing in mouse xenograft models of **ALK-fusion non-small cell lung cancer** treated with the ALK inhibitor **alectinib**. - In those models, steady dosing gave the strongest immediate tumor shrinkage, whereas fluctuating doses delayed the emergence of **drug resistance**. - Treatment regimens that alternated between even and uneven dosing achieved a balance: tumor control comparable to steady dosing while better preserving sensitivity to the drug. - The observed effects related to the shapes of **dose-response** functions, implying that measured dose-response curves can help decide when to keep doses steady or allow fluctuations. - The work expands regimen-design thinking by showing that intentional temporal dose variation can be used to navigate the tradeoff between immediate tumor reduction and long-term maintenance of drug sensitivity. - Findings are preclinical (mouse xenografts) and specific to ALK inhibition with alectinib in the reported models; the commentary highlights the potential to inform optimization of clinical schedules but does not report clinical trial results.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliation * 1 Department of Pharmacology, Computational Medicine Program, UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. * PMID: **42682083** * DOI: [ 10.1158/0008-5472.CAN-26-2187 ](https://doi.org/10.1158/0008-5472.can-26-2187) Item in Clipboard # Varying Cancer Drug Doses to Balance Tumor Control and Resistance Evolution Amy E Pomeroy et al. Cancer Res. 2026. Show details Display options Display options Format Abstract PubMed PMID Cancer Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cancer+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Cancer+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42682083/) . 2026 Sep 2;86(17):4195-4196. doi: 10.1158/0008-5472.CAN-26-2187. ### Authors [Amy E Pomeroy](https://pubmed.ncbi.nlm.nih.gov/?term=Pomeroy+AE&cauthor_id=42682083)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42682083/#short-view-affiliation-1 "Department of Pharmacology, Computational Medicine Program, UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina."), [Adam C Palmer](https://pubmed.ncbi.nlm.nih.gov/?term=Palmer+AC&cauthor_id=42682083)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42682083/#short-view-affiliation-1 "Department of Pharmacology, Computational Medicine Program, UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.") ### Affiliation * 1 Department of Pharmacology, Computational Medicine Program, UNC Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. * PMID: **42682083** * DOI: [ 10.1158/0008-5472.CAN-26-2187 ](https://doi.org/10.1158/0008-5472.can-26-2187) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract The effectiveness of any cancer therapy depends on its dose and its treatment schedule. A potential third dimension of regimen design is whether intentional fluctuations in administered dose might improve treatment outcomes. In this issue, West and colleagues demonstrate that dose fluctuations can alter both tumor drug response and the evolution of drug resistance, in ways related to the shapes of dose-response functions. In mouse xenograft models of ALK-fusion non-small cell lung cancer treated with the ALK inhibitor alectinib, steady dosing produced the best immediate tumor response, but fluctuations in dose were better at delaying the evolution of drug resistance. Treatment schedules that switched between even and uneven dosing navigated this tradeoff, achieving comparable tumor control with steady dosing while better preserving drug sensitivity. By showing how dose-response measurements can guide when doses should remain steady or fluctuate, this work expands how cancer treatment schedules might be optimized. See related article by West et al., p. 4434. ©2026 American Association for Cancer Research. 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