Cooling-Mediated Protection from Chemotherapy Drug-Induced Cytotoxicity in Human Keratinocytes by Inhibition of Cellular Drug Uptake

October 2020 in “ PLoS ONE ”

Christopher Dunnill, Khalidah Ibraheem, Michael Peake, Myria Ioannou, Megan A. Palmer, Adrian L. Smith, Andrew Collett, Nikolaos T. Georgopoulos

scalp cooling chemotherapy-induced alopecia doxorubicin epirubicin anthracyclines human keratinocytes hair follicle-derived primary keratinocytes

Studysummary This study found that scalp cooling markedly reduces cellular uptake of anthracycline drugs in human keratinocytes, partially explaining its protective effect against chemotherapy-induced cytotoxicity.

Our plain-language summary. Not medical advice or a treatment recommendation. Consult a qualified healthcare professional before changing treatment. Full disclaimer

The study investigated the protective effects of cooling on human keratinocytes against cytotoxicity induced by chemotherapy drugs doxorubicin and epirubicin. Cooling the cells to 22°C and 18°C significantly reduced the cellular uptake of these drugs, with up to an 8-fold reduction, thereby decreasing their cytotoxic effects. The research demonstrated that cooling was more effective at 18°C, particularly in primary NHEK cells and outer root sheath keratinocyte (ORSK) cultures, which are relevant to hair follicles. These findings suggested that cooling could protect hair follicles from chemotherapy-induced damage, supporting the clinical efficacy of scalp cooling in preventing chemotherapy-induced alopecia.

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Research cited in this study

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research CDK4/6 Inhibition Mitigates Stem Cell Damage in a Novel Model for Taxane-Induced Alopecia

58 citations , September 2019 in “EMBO Molecular Medicine”

This study found that the CDK4/6 inhibitor palbociclib may protect human hair follicles from the damaging effects of taxane chemotherapy by inducing G1 arrest in stem/progenitor cells.

research A Clinical and Biological Guide for Understanding Chemotherapy-Induced Alopecia and Its Prevention

38 citations , September 2017 in “Oncologist”

This source reports that scalp cooling is currently the only safe and FDA-cleared method to potentially reduce chemotherapy-induced hair loss, with about a 50% chance of maintaining sufficient hair to avoid needing a wig.

research Oxidative Damage Control in a Human Mini-Organ: Nrf2 Activation Protects Against Oxidative Stress-Induced Hair Growth Inhibition

58 citations , October 2016 in “Journal of Investigative Dermatology”

This study found that activating Nrf2 in human hair follicles significantly reduced oxidative stress, lipid peroxidation, and protected against hair growth inhibition, suggesting a protective role for Nrf2 against redox insult in this context.

research Testing Chemotherapeutic Agents in the Feather Follicle Identifies a Selective Blockade of Cell Proliferation and a Key Role for Sonic Hedgehog Signaling in Chemotherapy-Induced Tissue Damage

30 citations , September 2014 in “Journal of Investigative Dermatology”

This study found that certain chemotherapeutic agents, such as cyclophosphamide, disrupt feather formation and induce hair loss in mice by inhibiting cell proliferation through sonic hedgehog gene downregulation.

research Efficacy of Interventions for Prevention of Chemotherapy-Induced Alopecia: A Systematic Review and Meta-Analysis

110 citations , August 2014 in “International journal of cancer”

This study found that scalp cooling significantly reduced the risk of chemotherapy-induced alopecia in breast cancer patients, while topical minoxidil and other interventions did not show significant efficacy.

research Pathobiology of Chemotherapy-Induced Hair Loss

218 citations , January 2013 in “The Lancet Oncology”

This review discusses the pathobiology of chemotherapy-induced alopecia and highlights challenges in managing it, reporting no new clinical results and emphasizing the need for well-designed preclinical models to develop effective treatments.

Presentation, Impact and Prevention of Chemotherapy-Induced Hair Loss: Scalp Cooling Potentials and Limitations