Dermatologic Toxicities Associated With Novel Pan-RAS/RAF Inhibitors.
J Cutan Pathol 2026 Jun 04. [Online ahead of print]

Abstract

BACKGROUND

The mitogen-activated protein kinase (MAPK) pathway plays a key role in cell-cycle regulation and tumor progression in cancer. Dermatologic toxicities (DTs) to newer pan-RAS (RMC-6236) and pan-RAF (LXH254/naporafenib) inhibitors are emerging. Therefore, knowledge of the morphologic patterns of DTs from pan-RAS/RAF inhibitors will enable quick diagnosis and appropriate management.

METHODS

The clinical and histologic features of patients treated with pan-RAS or pan-RAF inhibitors for advanced stage RAS mutated malignancies were retrospectively reviewed.

RESULTS

Associated DTs were identified in eight patients treated with either pan-RAS (n = 4) or pan-RAF (n = 4) plus MEK/ERK inhibitors for RAS mutated tumors (colorectal, lung, pancreatic, thyroid, melanoma). The patients ranged from 37 to 72 years of age. Five patients had initial clinical presentation of an acneiform eruption complicated by ulceration, flaccid vesicles, or diffuse exfoliative erythroderma. Maculopapular eruption, purpuric patches and papules, and eruptive dark nevi were the other clinical presentations. Skin biopsies were primarily inflammatory with histopathologic features of suppurative folliculitis (n = 2), dermal hypersensitivity reaction (n = 2), subcorneal acantholytic dermatosis (n = 1), subcorneal pustules (n = 1), ulcer (n = 1), and eruptive nevi (n = 1).

CONCLUSIONS

Treatment with novel pan-RAS/RAF inhibitors exhibits a spectrum of DTs that exhibit some overlap with small molecule inhibitors that target the MAPK pathway.

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Authors+Show Affiliations

He LJDepartment of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Hegazy SDepartment of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Aung PPDepartment of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Nagarajan PDepartment of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Muhaj F0000-0001-7346-8809Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Choksi ANDepartment of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ciurea AMDepartment of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Nelson KCDepartment of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ivan DDepartment of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cabala CAT0000-0001-7422-0661Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Prieto VG0000-0001-9204-7161Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Curry JLDepartment of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

42244177