Paclitaxel Induces Epidermal Molecular Changes and Produces Subclinical Alterations in the Skin of Gynecological Cancer Patients

Abstract

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.

Paclitaxel alters melanogenesis and causes pigmentation in the skin of gynecological cancer patients

“…The project was approved by the Research Ethics Committee of Valencia University Clinical Hospital and further authorized by the Valencian Regional Ministry of Health. This study included patients from a previously published paper, which shares the sample and clinical design but measures different parameters [25]. The patient's clinical features are in Table 1, and inclusion and exclusion criteria can be found in [25].…”

“…This study included patients from a previously published paper, which shares the sample and clinical design but measures different parameters [25]. The patient's clinical features are in Table 1, and inclusion and exclusion criteria can be found in [25]. Patients' data in Table 1 include classification of the tumor by grade and stage.…”

Increased paclitaxel recovery from Taxus baccata vascular stem cells using novel in situ product recovery approaches

“…Therefore, current production of paclitaxel is mainly achieved by either plant cell–tissue cultivation or less sustainable semi-synthesis from more abundant precursors extracted by forest harvest (Kusari et al 2014 ). The current demand for paclitaxel, with global sales at up to 1 billion US dollars per year (Malik et al 2011 ; Precedence Research 2022 ), is likely to increase, as the applications for this key pharmaceutical in the treatment of atherosclerosis (Shiozaki et al 2016 ), skin maladies (Montero et al 2022 ) and potentially, neurodegenerative diseases (Ballatore et al 2007 ) continue to expand. Therefore, security in the supply of this WHO designated essential is a pivotal issue.…”

Keratinocyte Piezo1 drives paclitaxel-induced mechanical hypersensitivity

“…Paclitaxel-induced pain has been attributed to accumulation of the drug in the dorsal root ganglia and spinal cord, where it damages peripheral and central neurons 3 . However, paclitaxel also accumulates at high levels in the skin, often leading to severe dermatological reactions, such as inflammatory rashes, blistering lesions, and hyperpigmentation [4][5][6] . Despite this known accumulation, the specific impact of paclitaxel on the initial transduction and/or amplification of sensory stimuli in the epidermis remains unexplored.…”