Search Results (12)

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Background: Condyloma acuminata (CA) are dysplastic lesions caused by human papillomavirus (HPV) infection. Condylomata acuminata are common in Human Immunodeficiency Virus- (HIV) infected individuals and have been linked to HIV transmission. Current therapeutic options for CA encompass laser, cryotherapy, imiquimod, sinecatechins, podophyllotoxin, and trichloroacetate. These topical therapies have limitations caused by significant local skin reactions, high recurrence rates, prolonged application times, and, in some cases, a supposed lower efficacy in people living with Human Immunodeficiency Virus (PLWH). Previous studies evaluated the effect in the CA treatment of tirbanibulin 1% ointment since it is a synthetic antiproliferative drug approved for the topical treatment of actinic keratoses, acting in two distinct ways: it inhibits microtubule polymerization and Src kinase signaling. Human papilloma virus can up-regulate the kinases Src and Yes, so the tirbanibulin efficient treatment of CA may be due to the suppression of Src kinase signaling. Methods: Here, we present for the first time a retrospective case series of three PLWHIV affected by CA. Case: The patients experienced variable outcomes, with complete resolution of smaller condylomas for 2 out of 3 patients. Adverse events were local and of mild to moderate severity, lasting one week or less. Conclusions: While in need of larger studies, it is possible to hypothesize tirbanibulin 1% ointment as a therapeutic alternative for people living with HIV, especially for condylomas smaller than 1 cm in size. Full article

Background/Objectives: People living with HIV (PLWH) are more susceptible than immunocompetent people to non-melanoma skin cancers. These tumors can arise de novo or from precancerous lesions, such as actinic keratosis (AKs). The management of AKs in PLWH has not been widely discussed in the literature. More specifically, the efficacy of the treatment of AKs in PLWH with modern topical drugs, such as tirbanibulin, is limited. The present work aims to evaluate the response rate to the intervention with tirbanibulin 1% ointment for treating AKs in PLWH. Methods: We retrospectively collected the data of the PLWH who visited the Dermatology Department of the Policlinico Riuniti (Foggia, Italy) between September 2023 and September 2024. PLWH who received the diagnosis of AKs and underwent treatment with tirbanibulin 1% ointment were studied. To assess the severity of AKs, the number of AKs and the AKs’ area and severity index (AKASI) score were calculated at the time of diagnosis (T0) and after treatment (T1). Results: Ten PLWH were found to have AKs and received topical therapy with tirbanibulin 1% ointment. On average, at T0, the number of lesions was 8.2 and the AKASI score was 4.20; at T1, the number of AKs was 1.7 and the AKASI score was 1.5. Only two patients reported a mild inflammatory reaction to applying tirbanibulin 1% ointment. Conclusions: The rate of satisfactory responses was in line with a recent multicentric Italian study performed on immunocompetent patients. Our results confirm the efficacy and tolerability of tirbanibulin 1% ointment in treating AKs in PLWH in particular. Full article

Background and Objectives: Actinic keratosis (AK) is a precancerous cutaneous lesion driven by chronic ultraviolet (UV) exposure, often coexisting with features of photoaging, such as wrinkles and pigmentary irregularities. Recent evidence suggests that treatments for AK may also counteract photoaging through shared molecular pathways, including oxidative stress and inflammation. This narrative review explores the dual benefits of AK therapies, highlighting their potential anti-aging and skin-lightening effects, and implications for improving skin appearance alongside lesion clearance. Materials and Methods: The literature was analyzed to assess the efficacy, mechanisms, and cosmetic outcomes of commonly used AK treatments, including topical agents (5-fluorouracil (5-FU), imiquimod, diclofenac, and tirbanibulin), and photodynamic therapy (PDT). Studies highlighting their effects on photoaged skin, collagen remodeling, pigmentation, and patient satisfaction were reviewed. Results: PDT emerged as the most validated treatment, demonstrating improved collagen synthesis, skin texture, and pigmentation. 5-FU showed remodeling of the dermal matrix and increased procollagen levels, but local skin reactions represent a major limitation. Imiquimod enhanced dermal fibroplasia and reduced solar elastosis, while diclofenac provided mild photodamage improvements with minimal adverse effects. Tirbanibulin showed promising aesthetic outcomes, including skin lightening and a reduction in mottled pigmentation, with favorable tolerability. Conclusions: AK therapies offer a dual-purpose strategy, addressing both precancerous lesions and cosmetic concerns associated with photoaging. While PDT remains the gold standard, emerging agents like tirbanibulin ointment exhibit substantial potential. Future research should focus on optimizing treatment protocols and evaluating long-term cosmetic outcomes to enhance patient satisfaction and compliance. Full article

Introduction: Actinic keratosis (AK) is a widespread pre-cancerous skin condition that may evolve to squamous cell carcinoma, a non-melanoma skin cancer, which is able to become locally invasive and metastatic. Thus, it is important to treat AK. Methods: We conducted a cost-effectiveness analysis for the field-directed therapeutic approaches: local application of drugs containing 5-fluorouracil, both alone at a 4% concentration and associated to 10% salicylic acid at a 0.5% concentration (0.5% 5-FU + 10% SA cut. sol.); diclofenac-hyaluronic acid gel; imiquimod, both at 3.75% and 5% (5% IMQ cream) concentrations; and tirbanibulin ointment. The effectiveness data were abstracted from the literature. The cost-effectiveness analysis was performed by considering the prices reported by Agenzia Italiana del Farmaco (AIFA) for each medicine. Results: We obtained the total cost for each treatment by computing the cost of a single treatment for its duration. Application of 0.5% 5-FU + 10% SA cut. sol. appeared as the most convenient approach, as it was more effective and less expensive than all treatments except for 5% IMQ cream. For this last option, the incremental cost/effectiveness ratio analysis showed that a modest gain in effectiveness has a cost of EUR 7.94, therefore making it less cost effective. Full article

Background and Objectives: Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the face and scalp in adults. It has demonstrated good efficacy, an adequate safety profile and excellent patient adherence in the phase 3 clinical trials, however data about its real-life efficacy and safety are lacking. Here we report the experience of the dermatology unit of the University Hospital of Messina. Materials and Methods: We performed a spontaneous open-label, prospective non-randomized study to assess the effectiveness and safety of tirbanibulin 1% ointment for the treatment of 228 AKs in 38 consecutive patients—28 males (73%) and 10 females (26%)—aged between 52 and 92 years (mean age: 72 ± 8.92 years). Results: Total clearance was recorded in 51% of lesions, while partial clearance was recorded in 73% of lesions. An excellent tolerability profile and high compliance rate were observed, with no treatment discontinuation due to the onset of adverse events. Conclusion: Our real-life experience confirms the effectiveness and safety of tirbanibulin ointment for the treatment of AKs. Full article

Background: Actinic keratosis is a common precancerous skin lesion that can progress into invasive squamous cell carcinomas. Many topical treatments for actinic keratoses often have poor tolerability and prolonged duration. Tirbanibulin is a novel synthetic drug with potent antitumor and antiproliferative activities. Methods: We conducted a single-center, prospective and observational study using tirbanibulin ointment on a 25 cm² area for 5 consecutive days on 30 participants with AKs on the face or scalp. They were followed for at least 57 days to assess the safety profile and efficacy of the drug as well as treatment satisfaction. We evaluated six signs of local skin reaction (LSR): erythema, scaling, crusting, swelling, blisters/pustules, and erosions/ulcerations, grading the severity as mild, moderate, or severe. The effectiveness was evaluated both clinically and dermoscopically. The treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4). Results: On day 57, 70% of the patients showed a complete clinical and dermoscopic response. The highest scores obtained from the TSQM 1.4 were more evident in the convenience and side effects domains. Most LSRs, including erythema (83.3%), scaling (30%), and swelling (3.3%), occurred on day 8 but resolved spontaneously. Conclusion: Tirbanibulin is a viable therapeutic option with a short regimen treatment and good tolerability, which favors therapy adherence. Full article

Skin cancer is an overarching label used to classify a variety of cutaneous malignancies. Surgical excision procedures are the commonly used treatments for these lesions; however, the choice to perform operative intervention may be influenced by other factors. Established research and literature suggest that topical treatments limit the need for surgical intervention and its commonly associated adverse effects, including infection and scarring. In addition, the growing indications for the usage of topical therapies in BCC treatment, as well as their increased availability and therapeutic options, allow for their greater applicability in the dermatology clinic. Certain topical therapies have been highlighted in research, especially those targeting basal cell carcinoma (BCC) and actinic keratosis (AK). There is also a clear correlation between cost and treatment outcomes, considering BCC’s ever-growing prevalence and the proportion of excised lesions being reported as malignant. This review will discuss BCC and AK lesion criteria that result in the most successful outcomes using topical treatments, then highlight the various topical treatment options, and finally address their clinical significance moving forward. Full article

Background: Actinic keratosis (AK) is a cutaneous lesion resulting from the proliferation of atypical epidermal keratinocytes caused by long-term exposure to ultraviolet radiation. AK may progress to cutaneous squamous cell carcinoma (cSCC) and therefore is often treated with topical agents such as 5-fluorouracil, diclofenac, imiquimod, and photodynamic therapy. Tirbanibulin has been approved based on two phase III trials in the USA. However, real-world evidence for tirbanibulin is absent. Methods: This was a single-centre study of adult patients with clinically typical, visible AK on the face or scalp treated with tirbanibulin 1% ointment. Treatment was administered as per label once daily for 5 consecutive days on the same lesions or field. Treatment outcomes were assessed 4 weeks after treatment, with additional optional assessments conducted at later time points. Efficacy was measured using the actinic keratosis area and severity index (AKASI) and digital dermoscopy. Results: A total of 33 patients were treated of whom 30 were analysed. The median AKASI score was 5.6 (1.4–11) pre-treatment and 1.2 (0–7.4) post-treatment (p < 0.0001). Complete clearance as defined by AKASI scores less than 1 was achieved in 47% (n = 14) and 57% (n = 13) at the first and second follow-up, respectively. All local reactions resolved spontaneously and without sequelae. The most common local reactions were erythema (80%, n = 26) and flaking or scaling (43%, n = 13). Conclusions: Tirbanibulin 1% ointment significantly and rapidly reduced the AKASI score in a real-world setting. The complete clearance rates were in line with those observed in the two pivotal trials. Full article

Plaque-type psoriasis is a common skin disorder. Tirbanibulin (KX01) is a new Src kinase inhibitor with potent antiproliferative activity against keratinocytes and has been approved for treatment of actinic keratosis. This Phase I study investigates the safety and activity of KX01 ointment in patients with plaque-type psoriasis. We recruited 28 patients from two medical centers in Taiwan. This study was performed in four stages. Double-blind treatments were randomized in stages I (KX01 0.01% + placebo, two rounds of two-week treatment) and II (KX01 0.1% + placebo, four weeks) and open-labelled in stages III (KX01 1%, five days) and IV (KX01 1%, five days weekly for four weeks). The safety, tolerability, KX01 concentration, target area score, physician global assessment, and disease relapse were determined. Most treatment-emergent adverse events were mild-to-moderate application site reactions. Three (50.0%) subjects from the stage IV group showed ≥50% reduction in the target area score (TAS50), while two subjects (33.3%) showed a clinically meaningful improvement in the physician global assessment score. KX01 0.01%, 0.1%, and 1% were safe and well-tolerated. KX01 1% at four weeks showed a promising activity for the treatment of plaque-type psoriasis. Full article

Recent evidence suggests that numerous similarities exist between the genomic landscapes of both conjunctival and cutaneous melanoma. Since alterations of several components of the MAP kinases, PI3K/mTOR, and cell cycle pathways have been reported in conjunctival melanoma, we decided to assess the sensitivity of conjunctival melanoma to targeted inhibition mostly of kinase inhibitors. A high content drug screening assay based on automated fluorescence microscopy was performed in three conjunctival melanoma cell lines with different genomic backgrounds with 489 kinase inhibitors and 53 other inhibitors. IC50 and apoptosis induction were respectively assessed for 53 and 48 compounds. The genomic background influenced the response to MAK and PI3K/mTOR inhibition, more specifically cell lines with BRAF ^V600E mutations were more sensitive to BRAF/MEK inhibition, while CRMM2 bearing the NRAS^Q61L mutation was more sensitive to PI3k/mTOR inhibition. All cell lines demonstrated sensitivity to cell cycle inhibition, being more pronounced in CRMM2, especially with polo-like inhibitors. Our data also revealed new vulnerabilities to Hsp90 and Src inhibition. This study demonstrates that the genomic background partially influences the response to targeted therapy and uncovers a large panel of potential vulnerabilities in conjunctival melanoma that may expand available options for the management of this tumor. Full article

Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for key treatments for AK of the face and scalp, including the novel 5-day tirbanibulin 1% ointment. MEDLINE, PubMed, Embase, Cochrane Library, clinical trial registries and regulatory body websites were searched. The review included 46 studies, of which 35 studies included interventions commonly used in Europe and were sufficiently homogenous to inform a Bayesian network meta-analysis of complete clearance against topical placebo or vehicle. The network meta-analysis revealed the following odds ratios and 95% credible intervals: cryosurgery 13.4 (6.2–30.3); diclofenac 3% 2.9 (1.9–4.3); fluorouracil 0.5% + salicylic acid 7.6 (4.6–13.5); fluorouracil 4% 30.3 (9.1–144.7); fluorouracil 5% 35.0 (10.2–164.4); imiquimod 3.75% 8.5 (3.5–22.4); imiquimod 5% 17.9 (9.1–36.6); ingenol mebutate 0.015% 12.5 (8.1–19.9); photodynamic therapy with aminolevulinic acid 24.1 (10.9–52.8); photodynamic therapy with methyl aminolevulinate 11.7 (6.0–21.9); tirbanibulin 1% 11.1 (6.2–20.9). Four sensitivity analyses, from studies assessing efficacy after one treatment cycle only, for ≤25 cm² treatment area, after 8 weeks post-treatment, and with single placebo/vehicle node confirmed the findings from the base case. Safety outcomes were assessed qualitatively. These results suggest that tirbanibulin 1% offers a novel treatment for AK, with a single short treatment period, favourable safety profile and efficacy, in line with existing topical treatments available in Europe. Full article