Skin Extracellular Matrix Breakdown Following Paclitaxel Therapy in Patients with Chemotherapy-Induced Peripheral...

Area of Science:

• Oncology
• Neurology
• Dermatology

Background:

• Paclitaxel chemotherapy can cause peripheral neuropathy, a significant side effect impacting cancer patients' quality of life.
• Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting toxicity of paclitaxel treatment.
• Previous research suggests a role for skin changes in CIPN, with studies in zebrafish and rodents.

Purpose of the Study:

• To investigate the impact of paclitaxel therapy on the skin of breast cancer patients experiencing CIPN.
• To correlate patient-reported CIPN symptoms with objective skin changes, including nerve fiber density and molecular alterations.
• To explore the molecular mechanisms underlying skin alterations in CIPN.

Main Methods:

• Neurological examinations and quality of life questionnaires were administered to assess CIPN symptoms.
• Skin punch biopsies were used for intraepidermal nerve fiber (IENF) density evaluation.
• RNA sequencing, MMP-13 immunostaining, and transmission electron microscopy were employed to analyze molecular and ultrastructural skin changes.

Main Results:

• No significant difference in IENF density was observed between patients with and without CIPN, despite reported symptoms.
• Significantly upregulated Matrix-Metalloproteinase 13 (MMP-13) was detected in the skin of CIPN patients.
• Differential gene expression was noted in pathways related to extracellular matrix, microtubules, cell cycle, and nervous system regulation. Ultrastructural analysis revealed changes in collagen and basement membrane.

Conclusions:

• CIPN can manifest without a reduction in IENF density, suggesting alternative mechanisms.
• Skin remodeling, indicated by altered extracellular matrix and basement membrane structures, plays a crucial role in paclitaxel-induced peripheral neuropathy.
• Upregulation of MMP-13 in the skin is a key molecular event associated with CIPN.