Pathomechanisms of Dermatologic Adverse Effects of Targeted Therapies in Pediatric Solid Tumors: A Narrative Review
- 1Pediatric Center, Semmelweis University, Budapest, H-1094 Hungary
- 2Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, H-1085 Hungary
Abstract
Purpose of Review: Targeted anticancer therapies have transformed the treatment of pediatric solid tumors but are associated with a distinct spectrum of dermatologic adverse effects that may impair quality of life and compromise treatment adherence. This review summarizes the molecular and cellular mechanisms underlying these toxicities and integrates current mechanistic evidence with their clinical manifestations, prevention, and management.
Recent Findings: Recent mechanistic and clinical evidence indicates that targeted therapy–related cutaneous toxicities arise from pathway-specific disruption of epidermal, vascular, and immune homeostasis. Major mechanisms include paradoxical MAPK activation during BRAF inhibition; impaired keratinocyte proliferation, differentiation, and barrier function during MEK, EGFR, and mTOR inhibition; endothelial and epidermal injury associated with VEGFR-targeting multikinase inhibitors; and loss of immune tolerance during immune checkpoint blockade. These mechanisms contribute to characteristic phenotypes including papulopustular eruptions, xerosis, paronychia, hand–foot skin reaction, pigmentary alterations, and immune-mediated dermatoses. Pediatric-specific mechanistic and prospective dermatologic data remain limited, and evidence for several newer targeted agents is largely extrapolated from adult studies.
Summary: Dermatologic toxicities of targeted therapies reflect predictable perturbations of signaling pathways that are also essential for normal skin homeostasis. Understanding these pathomechanisms may facilitate early recognition, mechanism-based prevention and treatment, and preservation of anticancer therapy. Pediatric-specific prospective studies and standardized dermatologic outcome reporting are needed.
Related
- Advances in targeted therapies for pediatric tumors
- RPE-Targeted Laser Therapies for Central Serous Chorioretinopathy: Sublethal Modulation Versus Selective Injury and Repair—A Narrative Review
- Long-Term Cardiovascular, Thromboembolic, and Malignancy Safety of Janus Kinase (JAK) Inhibitors in Dermatologic and Rheumatologic Populations: A Narrative Comparative Review.
- Magnesium in Skin Aging, Wound Healing, and Some Specific Dermatologic Disorders: A Narrative Review on Biological Mechanisms, Clinical Evidence, and Therapeutic Perspectives
- Hippo pathway in cancer ferroptosis: from mechanism insights to targeted therapies
BibTeX
@article{klaus2026pathomechanisms,
title = {{Pathomechanisms of Dermatologic Adverse Effects of Targeted Therapies in Pediatric Solid Tumors: A Narrative Review}},
author = {Laura Klaus and Edit Brückner and Péter B. Botos and Márta Medvecz and Péter Holló and Attila J. Szabó and Sarolta Kárpáti and Miklós Garami},
journal = {Current Oncology Reports},
year = {2026},
month = nov,
doi = {10.1007/s11912-026-01854-8},
url = {https://doi.org/10.1007/s11912-026-01854-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pathomechanisms of Dermatologic Adverse Effects of Targeted Therapies in Pediatric Solid Tumors: A Narrative Review
AU - Laura Klaus
AU - Edit Brückner
AU - Péter B. Botos
AU - Márta Medvecz
AU - Péter Holló
AU - Attila J. Szabó
AU - Sarolta Kárpáti
AU - Miklós Garami
PY - 2026
DA - 2026/11/05
JO - Current Oncology Reports
DO - 10.1007/s11912-026-01854-8
UR - https://doi.org/10.1007/s11912-026-01854-8
AB - Purpose of Review: Targeted anticancer therapies have transformed the treatment of pediatric solid tumors but are associated with a distinct spectrum of dermatologic adverse effects that may impair quality of life and compromise treatment adherence. This review summarizes the molecular and cellular mechanisms underlying these toxicities and integrates current mechanistic evidence with their clinical manifestations, prevention, and management. Recent Findings: Recent mechanistic and clinical evidence indicates that targeted therapy–related cutaneous toxicities arise from pathway-specific disruption of epidermal, vascular, and immune homeostasis. Major mechanisms include paradoxical MAPK activation during BRAF inhibition; impaired keratinocyte proliferation, differentiation, and barrier function during MEK, EGFR, and mTOR inhibition; endothelial and epidermal injury associated with VEGFR-targeting multikinase inhibitors; and loss of immune tolerance during immune checkpoint blockade. These mechanisms contribute to characteristic phenotypes including papulopustular eruptions, xerosis, paronychia, hand–foot skin reaction, pigmentary alterations, and immune-mediated dermatoses. Pediatric-specific mechanistic and prospective dermatologic data remain limited, and evidence for several newer targeted agents is largely extrapolated from adult studies. Summary: Dermatologic toxicities of targeted therapies reflect predictable perturbations of signaling pathways that are also essential for normal skin homeostasis. Understanding these pathomechanisms may facilitate early recognition, mechanism-based prevention and treatment, and preservation of anticancer therapy. Pediatric-specific prospective studies and standardized dermatologic outcome reporting are needed.
SN - 1523-3790
SN - 1534-6269
ER -