Cutaneous Toxicities of Targeted Cancer Therapies

Targeted agents directed against kinases and growth-factor receptors have transformed the treatment of many malignancies but frequently induce skin, hair and nail abnormalities. Inhibitors of BRAF and MEK used in melanoma, epidermal growth factor receptor (EGFR) inhibitors in lung and colorectal cancers, and multikinase agents in renal and thyroid carcinomas all disrupt signalling pathways integral to epidermal homeostasis. Common manifestations include maculopapular and papulopustular eruptions, xerosis with pruritus, photosensitivity, hand–foot skin reactions and paronychia. Paradoxical activation of RAS-MAPK signalling by BRAF inhibitors underlies the emergence of hyperkeratotic lesions and keratoacanthomas, while EGFR blockade impairs keratinocyte proliferation and follicular differentiation, precipitating acneiform rash. Chronic cutaneous toxicity can compromise quality of life and lead to dose reductions or discontinuation of otherwise efficacious therapy. Recognition of clinical patterns, understanding of underlying molecular mechanisms and adoption of prophylactic measures—such as moisturisers, photoprotection and topical corticosteroids—are essential. A multidisciplinary approach involving dermatologists and oncologists underpins evolving management guidelines and fosters the safe continuation of life-prolonging regimens.

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Cutaneous Toxicities of Targeted Cancer Therapies publication trend

The graph below shows the total number of articles in cutaneous toxicities of targeted cancer therapies across all publications each year (not limited to Nature Index journals).

Technical terms

BRAF inhibitor: Small molecule targeting mutant BRAF kinase, used in melanoma, often causing paradoxical activation of MAPK in wild-type cells.

EGFR inhibitor: Agent blocking epidermal growth factor receptor, employed in lung and colorectal cancers, commonly inducing acneiform rash.

MAPK pathway: Mitogen-activated protein kinase cascade, central to cell proliferation and differentiation; its dysregulation underlies proliferative skin lesions.

DRESS syndrome: Drug Reaction with Eosinophilia and Systemic Symptoms; severe cutaneous eruption with systemic involvement, requiring prompt steroid therapy.

References

1. Cutaneous Side Effects of BRAF Inhibitors in Advanced Melanoma: Review of the Literature. Dermatology Research and Practice (2016).
2. RASopathic Skin Eruptions during Vemurafenib Therapy. PLOS ONE (2013).
3. Management of dermatologic adverse events from cancer therapies: recommendations of an expert panel. Anais Brasileiros de Dermatologia (2020).
4. Cutaneous adverse reactions in B-RAF positive metastatic melanoma following sequential treatment with B-RAF/MEK inhibitors and immune checkpoint blockade or vice versa. A single-institutional case-series. Journal for ImmunoTherapy of Cancer (2019).