Abstract
Simple SummarySkin toxicity is one of paclitaxel’s adverse effects. However, its real impact on the skin could be underestimated as these alterations can also appear asymptomatic. We have observed that paclitaxel modifies gene and protein expression of skin markers in a 3D epidermis model, and impairs physical, physiological, and biomechanical properties of the skin in gynecologic cancer patients. These subclinical alterations might be avoided by using prophylactic measures during treatment to prevent possible future adverse reactions.Background: Paclitaxel is a microtubule-stabilizing chemotherapeutic agent. Despite its widespread use, it damages healthy tissues such as skin. The goal of this study was to prove that the real impact of paclitaxel-induced skin toxicity could be underestimated because the adverse events might appear asymptomatic. Methods: Gynecological cancer patients were recruited. Skin parameters measurements were taken after three and six paclitaxel cycles. Measurements were conducted using specific probes which measure hydration, transepidermal water loss (TEWL), sebum, elasticity and firmness, erythema, roughness, smoothness, skin thickness, and desquamation levels. Further, a 3D epidermis model was incubated with paclitaxel to analyze gene and protein expression of aquaporin 3, collagen type 1, elastin, and fibronectin. Results: Paclitaxel induced alterations in the skin parameters with no visible clinical manifestations. Gynecological cancer patients under paclitaxel treatment had a decrease in hydration, TEWL, sebum, elasticity, and thickness of the skin, while erythema, roughness, and desquamation were increased. The molecular markers, related to hydration and the support of the skin layers, and analyzed in the 3D epidermis model, were decreased. Conclusions: Results suggest that paclitaxel modifies gene and protein expression of skin-related molecular markers, and impairs different physical, physiological, and biomechanical properties of the skin of cancer patients at a subclinical level.
Highlights
Taxanes are chemotherapeutic agents that produce antitumor activity by causing stabilization of microtubules, thereby inhibiting cell cycle progression [1]
Quantification was performed by densitometry and normalized to β-actin
Oncologic patients had decreased skin elasticity and firmness as shown by the lowered R parameters, which represent the state of the biomechanical elastic properties of the skin [56,57,58]. These results suggest that PTX-induced decrease in the skin elasticity and firmness might be mediated by its capacity to modulate molecular markers such as collagen type 1 (COL1), ELN, and FN1, which maintain the structure of the skin layers
Summary
Taxanes are chemotherapeutic agents that produce antitumor activity by causing stabilization of microtubules, thereby inhibiting cell cycle progression [1]. Is the prototype of the taxane family of antitumor compounds and binds to the β-tubulin subunit in the microtubule, leading to its stabilization and increasing microtubule polymerization [2]. This unique mechanism of action differentiates paclitaxel from other antimicrotubule agents such as vinca alkaloids or colchicine, which inhibit tubulin polymerization. Gynecological cancer patients under paclitaxel treatment had a decrease in hydration, TEWL, sebum, elasticity, and thickness of the skin, while erythema, roughness, and desquamation were increased. Conclusions: Results suggest that paclitaxel modifies gene and protein expression of skin-related molecular markers, and impairs different physical, physiological, and biomechanical properties of the skin of cancer patients at a subclinical level
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