The combination of oral and topical photoprotection with a standardized Polypodium leucotomos extract is beneficial against actinic keratosis.

INTRODUCTION: This study describes a prospective, multicentre, randomized controlled, open-label study with three arms aimed at studying the differences between: [Cnt], self-administered sun protection; [T], topical treatment; and [TO], topical + oral treatment; for the management of Actinic Keratosis (AK) in a cohort of subjects of advanced age displaying severe actinic damage (SAD). METHODS: Treatments administered to groups [T] and [TO] had a common component, which is a botanical extract, Fernblock, with demonstrated photoprotective activity. RESULTS: In total, 131 subjects were distributed randomly in the three groups, and followed up clinically at three separate time points, beginning of the study (t = 0) and after 6 and 12 months. Analysis of clinical data and examination using reflectance confocal microscopy (RCM) revealed that group [T] and [TO] displayed decreased clinical AK and field cancerization parameters, including the number of new lesions, and reduced the need for additional interventions in these patients. RCM revealed normalization of the keratinocyte layer. Improvements in AK and field cancerization parameters were greatest in the group [TO], suggesting that topical and oral photoprotection improves the clinical and anatomical outcome compared to control conditions. CONCLUSIONS: The combination of topical and oral immune photoprotection provides an advantage compared to topical photoprotection alone.

Family caregivers' experience of communication with nursing home staff from admission to end of life during the COVID-19 pandemic: A qualitative study employing a transitional perspective.

OBJECTIVES: Family caregivers' (FCs) caregiving in nursing home (NH) moves across 3 main phases: transitioning relatives to long-term care, worsening of a relative's conditions, and end of life; each phase brings specific challenges that FCs must confront. Moreover, during the COVID-19 pandemic, strict mandatory visitor restrictions affected communication modalities. This study explored FCs' experience of communication with NH staff during the COVID-19 pandemic from admission to end of life. METHODS: A descriptive qualitative study with inductive content analysis was performed in 7 Italian NHs from May to June 2021. NH managers purposively identified 25 FCs at different phases of their caregiving trajectory: transitional (i.e., admission in the previous 8 weeks, n = 8), deterioration-in-condition (i.e., acknowledged changes in care needs of their relative after trigger events, n = 10), and end-of-life phase (i.e., death expected in the next weeks or a few months, n = 7), who were interviewed. RESULTS: Regardless the phase of caregiving trajectory, what mattered most to FCs was the opportunity to have regular and sensitive discussions with health-care professionals. The need of in-person communication increased nearing death. The COVID-19 pandemic enhanced FCs' need to interact with health-care professionals they trusted. Knowledge of residents' preferences mitigated FCs' turbulent emotions throughout the overall caregiving trajectory. SIGNIFICANCE OF RESULTS: Findings suggest that in-person contacts should be prioritized and facilitated when possible, particularly at the end of life; nonetheless, meaningful communication can occur also through remote modalities. Investments in training health-care professionals about effective long-distance communication and supportive skills can help trusting relationships to be established. Open discussions about residents' care preferences should be encouraged.

HAP40 is a conserved central regulator of Huntingtin and a potential modulator of Huntington's disease pathogenesis.

Perturbation of huntingtin (HTT)'s physiological function is one postulated pathogenic factor in Huntington's disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT's conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, HAP40 strongly affected HTT's stability, as depletion of HAP40 significantly reduced the levels of endogenous HTT protein while HAP40 overexpression markedly extended its half-life. Conversely, in the absence of HTT, the majority of HAP40 protein were degraded, likely through the proteasome. Further, the affinity between HTT and HAP40 was not significantly affected by polyglutamine expansion in HTT, and contrary to an early report, there were no abnormal accumulations of endogenous HAP40 protein in HD cells from mouse HD models or human patients. Lastly, when tested in Drosophila models of HD, HAP40 partially modulated the neurodegeneration induced by full-length mutant HTT while showed no apparent effect on the toxicity of mutant HTT exon 1 fragment. Together, our study uncovers a conserved mechanism governing the stability and in vivo functions of HTT and demonstrates that HAP40 is a central and positive regulator of endogenous HTT. Further, our results support that mutant HTT is toxic regardless of the presence of its partner HAP40, and implicate HAP40 as a potential modulator of HD pathogenesis through its multiplex effect on HTT's function, stability and the potency of mutant HTT's toxicity.

The impact of COVID-19 pandemic in a cohort of Italian psoriatic patients treated with biological therapies.

BACKGROUND: The beginning of 2020 has been marked by COVID-19 pandemic, with a strong impact on several national health systems worldwide. OBJECTIVE: To describe the impact of COVID-19 pandemic in a cohort of Italian psoriatic patients treated with biologics. METHODS: A telephone survey was conducted in May 4-10 2020 about the Italian lockdown period (March 9-May 3 2020) in a cohort of psoriatic patients treated with biologics, asking about any exposure to COVID-19, disease status, continuation of therapy, work activity and psychological status through Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS) and Brief Resilience Scale (BRS). RESULTS: 226 patients were interviewed, with no COVID-19 positive cases. Sixty-three of 226 (27.9%) described worsening of the disease with a correlation to drug withdrawal [43/226 (19%)]. Correlation was also found between the worsening of psoriasis and HADS anxiety, HADS depression, BRS and PSS abnormal scores considered both as categorical and continuous variables. No correlation was found between worsening of psoriasis and work activity. CONCLUSION: Uncertainty about whether biologics could increase the risk of SARS-CoV-2 infection led to drug withdrawal with subsequent worsening of psoriasis. Moreover, psychological status also had a direct influence on the clinical course of the disease.

Satisfaction and attitudes toward systemic treatments for psoriasis: A cross-sectional study.

In psoriasis patients, satisfaction and patients' attitude toward treatment are heterogeneous depending on several factors and remain poorly investigated, although the availability of several new targeted therapeutic options. A multicentre cross-sectional investigation was conducted to estimate treatment satisfaction and attitudes (awareness, trust, and therapeutic alliance) in a large population of adult psoriasis patients undergoing a systemic biologic or non-biologic agent for moderate-to-severe plaque-type psoriasis. Patients' satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication II questionnaire and patients' attitudes toward treatment were evaluated using a Lickert scale. Results were related to patients' and treatment characteristics and therapeutic outcomes. The study included 899 psoriasis patients and demonstrated high-treatment satisfaction and positive attitudes toward systemic treatments, with greater influence of the perceived efficacy and the type of treatment. Biologic treatments and, in particular anti-IL17 agents showed higher results. More efforts in developing tools facilitating communication and exploring important aspects of patients' view are needed.

NRF2 activation by reversible KEAP1 binding induces the antioxidant response in primary neurons and astrocytes of a Huntington's disease mouse model.

Oxidative stress has been associated with pathogenesis in several diseases including Huntington's disease (HD), a neurodegenerative disorder caused by a mutation in the huntingtin gene. Oxidative stress induced reactive oxygen species (ROS) are normally controlled at the cellular level by the nuclear factor (erythroid-derived 2)-like 2 (NRF2) a transcription factor that regulates the expression of various antioxidants and detoxifying proteins. Normally NRF2 is largely inactivated in the cytoplasm by the Kelch-like ECH-associated protein 1 (KEAP1)/Cullin-3 (CUL3) mediated ubiquitination and subsequent proteosomal degradation. In the presence of ROS, KEAP1 sensor cysteines are directly or indirectly engaged resulting in NRF2 release, nuclear translocation, and activation of its target genes. Consequently the activation of NRF2 by a small-molecule drug may have the therapeutic potential to control oxidative stress by upregulation of the endogenous antioxidant responses. Here we attempted to validate the use of a reversible non-acidic KEAP1 binder (Compound 2) to activate NRF2 with better cellular activity than similar acidic compounds. When tested head to head with sulforaphane, a covalent KEAP1 binder, Compound 2 had a similar ability to induce the expression of genes known to be modulated by NRF2 in neurons and astrocytes isolated from wild-type rat, wild type mouse and zQ175 (an HD mouse model) embryos. However, while sulforaphane also negatively affected genes involved in neurotoxicity in these cells, Compound 2 showed a clean profile suggesting its mode of action has lower off-target activity. We show that Compound 2 was able to protect cells from an oxidative insult by preserving the ATP content and the mitochondrial potential of primary astrocytes, consistent with the hypothesis that neurotoxicity induced by oxidative stress can be limited by upregulation of innate antioxidant response.

Photodynamic therapy with 5-aminolevulinate patch for the treatment of superficial basal cell carcinomas.

5-Aminolevulinate (ALA) patches with red light (630-nm light source and a total light dose of 37 J/cm2 ) is an effective treatment indicated by food and drug administration (FDA) and european medicines agency (EMA) only for grade I to II actinic keratosis located on the scalp and face. Currently, there are no efficacy data on their use in the treatment of other types of epithelial neoplasms. We analyzed the efficacy of ALA patches in seven superficial basal cell carcinomas (sBCCs) that occurred in four patients. All lesions were treated with topical ALA patches. A complete response of all sBCCs was achieved at week 24 after treatment. Our study suggests that ALA patches for sBCCs have good efficacy rates and excellent safety profile.

5-Aminolaevulinic acid patch photodynamic therapy for the treatment of actinic keratoses: preliminary results from an Italian study in the real-life setting.

BACKGROUND: Photodynamic therapy (PDT) is recommended for both lesion and field therapy of actinic keratoses (AKs). The 5-aminolaevulinic acid (5-ALA) patch PDT is indicated for the treatment of isolated mild AKs (≤1.8 cm) on the face and bald scalp. It was demonstrated to be effective and safe in clinical trials with a good tolerability profile. METHODS: In this retrospective multicenter real-life study, 33 patients with a total of 99 AKs of the scalp, face, ears, and/or hands and 2 actinic cheilitis were treated with one treatment session of 5-ALA patch PDT with a red light source (total dose of 37 J/cm2). RESULTS: Overall, 12 weeks after treatment, 68/99 (69%) lesions were completely cleared. Complete response was obtained in 82% of AKs on the ears, 78% on the face, 57% on the hands, and 56% on the scalp and in the two actinic cheilitis. The treatment was very effective on grade I AKs, cleared in 87% of the cases and less efficient on grade II-III lesions, cleared in 47% of the cases. 5-ALA patch PDT was well tolerated with a good to excellent cosmetic outcome in 97% of the patients and with 94% of the patients being satisfied or very satisfied with the treatment. CONCLUSIONS: Our results confirm that 5-ALA patch PDT is a good option for AK treatment in clinical practice, it is easy to use, effective and well tolerated even in difficult-to-treat-areas. Moreover, it has an excellent cosmetic outcome.

Optimization of linear and cyclic peptide inhibitors of KEAP1-NRF2 protein-protein interaction.

Inhibition of KEAP1-NRF2 protein-protein interaction is considered a promising strategy to selectively and effectively activate NRF2, a transcription factor which is involved in several pathologies such as Huntington's disease (HD). A library of linear peptides based on the NRF2-binding motifs was generated on the nonapeptide lead Ac-LDEETGEFL-NH2 spanning residues 76-84 of the Neh2 domain of NRF2 with the aim to replace E78, E79 and E82 with non-acidic amino acids. A deeper understanding of the features and accessibility of the T80 subpocket was also targeted by structure-based design. Approaches to improve cell permeability were investigated using both different classes of cyclic peptides and conjugation to cell-penetrating peptides. This insight will guide future design of macrocycles, peptido-mimetics and, most importantly, small neutral brain-penetrating molecules to evaluate whether NRF2 activators have utility in HD.

Baricitinib: therapeutic potential for moderate to severe atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease mediated by multiple signals including janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Current therapeutic armamentarium consists of a limited number of drugs which may result in the insufficient management of AD. Preclinical evidence regarding inhibition of JAK/STAT led to the development of a promising class of therapeutics, namely, JAK inhibitors. Baricitinib, a novel JAK1/JAK2 inhibitor is currently under investigation in AD clinical trials. AREAS COVERED: This review offers an overview of Baricitinib and examines clinical efficacy and safety data in patients with moderate-to-severe AD. EXPERT OPINION: Baricitinib showed promising preliminary data in terms of efficacy in phase II and III trials, with a very rapid onset of response and great improvements of itch and sleep disturbances. These aforementioned aspects combined with the advantage of an oral formulation have reduced drug production costs compared to biologic agents and could lead to consideration of baricitinib as a first line systemic treatment. Also, in some countries, it could be a therapeutic option in the case of contraindication or failure of conventional systemic drugs prior to biologic therapies. Data related to long-term safety and efficacy will be important to refine the place-in-therapy of this drug.

Cohort analysis of safety and efficacy of vismodegib in Italian patients from the Phase II, multicenter STEVIE study.

Aim: To assess safety and efficacy of vismodegib in the Italian cohort from the SafeTy Events in VIsmodEgib study. Materials & methods: Data from Italian patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC were analyzed. Results: Among 182 Italian patients, adverse events occurred with similar incidence to the overall population. Overall response rate was 67.1% in laBCC, 20% in metastatic BCC; complete response rate was 33.1% overall and 37.4% in laBCC. Median time to response was 2 months in complete responders versus 3.6 months overall. Quality of life improved from baseline. Conclusion: In the Italian cohort of STEVIE, vismodegib showed a safety profile consistent with the whole population; older age did not affect safety or efficacy. ClinicalTrials.gov registration: NCT01367665.

Safety and efficacy of certolizumab pegol in a real-life cohort of patients with psoriasis and psoriatic arthritis.

Background: The aim of this observational study was to assess safety and efficacy of certolizumab pegol (CZP) in a real-life cohort of patients affected by psoriasis (PsO) and psoriatic arthritis (PsA), who had an inadequate response to previous systemic immunosuppressive treatments, with a follow-up of 24 weeks.Materials and methods: Twelve patients with PsO and PsA, referring to our Dermatology/Rheumatology combined outpatient clinic, were enrolled. Primary endpoints were safety and efficacy of CZP, defined as statistically significant improvement of DAPSA, clinical DAPSA and PASI. Secondary endpoints validated clinical and laboratory measures and patient-reported outcomes.Results: CZP injections were well-tolerated. We observed a rapid and significant improvement in all primary endpoints, in the 24-week treatment period of the study. We described positive effects of CZP in several domains, including joint and skin involvement, pain, patient and physician global assessment, physical function, and health-related quality of life. CZP was effective and safe in patients who were either naïve or previously unresponsive to other anti-TNFα. No difference was found in terms of efficacy and safety between patients treated with CZP monotherapy and patients in combination therapy with methotrexate.Conclusions: CZP was safe and effective in a real-life cohort of patients affected by PsO and PsA, who have had an inadequate response to previous systemic treatments.

Efficacy and safety of Vismodegib treatment in patients with advanced basal cell carcinoma and multiple comorbidities.

Basal cell carcinoma (BCC) is the most common malignancy in Caucasians, and its incidence is increasing. Most BCCs are treated surgically, nevertheless surgery is not an effective treatment for locally advanced or metastatic BCC. Alterations in hedgehog signaling pathway, a key regulator of cell growth and differentiation during development, are implicated in the pathogenesis of basal-cell carcinoma. Vismodegib is a small-molecule inhibitor of smoothened (SMO), a key component of the hedgehog (Hh) signaling pathway, administered in BCC patients, especially when surgery and radiotherapy treatments have failed. We report a series of eight elderly patients treated with vismodegib for advanced BCC and affected by concomitant multiple comorbidities. The efficacy and tolerability of vismodegib in patients with single and/or multiple comorbidities has been poorly studied. In our observation an overall high safety and tolerability has been observed over the course of treatment, with side effects of grade I and II and no changes in vital parameters, electrocardiography and echocardiogram. Vismodegib has been shown to be a safe and well tolerated treatment option for elderly patients affected by multiple comorbidities and advanced BCC.

Single versus two-treatment schedule of methyl aminolevulinate daylight photodynamic therapy for actinic keratosis of the face and scalp: An intra-patient randomized trial.

BACKGROUND: Efficacy of daylight-photodynamic therapy (DL-PDT) with methyl aminolaevulinate (MAL) has been reported to gradually decrease as the severity of actinic keratosis (AK) lesions increases. Repeated treatments have been suggested to increase the efficacy of DL-PDT. Aim of our pilot study was to evaluate the efficacy and tolerability of a single versus two-treatment schedule of MAL DL-PDT for the treatment of multiple AKs of the face/scalp in a prospective, intra-patient, comparison study. METHODS: Patients with multiple AKs of the face/scalp received a single treatment of MAL DL-PDT or 2 treatments, 1 week apart, on either half-side. Weather conditions and outdoor temperature were recorded during daylight exposure. Visual analog scale for pain was assessed immediately after each session, and severity of local skin reactions after 2 days. Treatment efficacy was evaluated at 3 months. RESULTS: Thirty-one patients with multiple AKs of the face/scalp were enrolled and completed the study. No significant difference was observed between single and two-treatment schedule in the lesion complete response rate for total AKs (80.7% vs 85.6%, p = 0.28) and for AKs divided by grade (grade I: 88.5% vs 89.2%, p = 0.79; grade II: 67.3% vs 71.0%, p = 0.71; grade III: 50.0% vs 55.6%, p≈1.00). Pain was significantly higher during the second session (p = 0.04). Local skin reactions were generally mild, but more severe after the first treatment (p < 0.01). CONCLUSIONS: The two-treatment schedule did not improve significantly the efficacy of MAL DL-PDT for AKs of the face and scalp as compared to the single-treatment. Alternative strategies might be recommended to optimize the efficacy of DL-PDT.

Secukinumab in moderate-to-severe plaque psoriasis: a multi-center, retrospective, real-life study up to 52 weeks observation.

OBJECTIVES: To evaluate efficacy and safety of the anti-IL-17 drug secukinumab in a real-life large cohort of patients with moderate-to-severe plaque psoriasis in Central Italy. METHODS: Multicenter, retrospective study with an observation period of up to 52 weeks. Efficacy was assessed by Psoriasis Area and Severity Index (PASI) score; clinical and laboratory examinations were performed at baseline and at weeks 4, 12, 24, 36, and 52. RESULTS: A 90% and a 100% PASI score reduction (PASI90 and PASI100) were reported in 67.5% and 55% of patients at week 12, respectively. A rapid improvement of skin lesions was observed particularly in young patients and in patients naïve to biologics: at week 4, the achievement of PASI90 and PASI100 was higher in younger patients (odds ratio [OR] 0.95, and 0.95; p = 0.003, and 0.005, respectively); PASI90 was achieved by 42.0% of patients naïve to biologics and by 17.0% of patients with prior exposure to biologics (PBT) (OR 0.24; p = 0.001); and PASI100 was reached by 25.5% of naïve patients and 9.8% of PBT (OR 0.28; p = 0.015).The drug was well tolerated. CONCLUSION: Secukinumab was effective in this real-life analysis, with rapid clinical improvement and long-term maintenance of results.

Clinical experience of imiquimod 3.75% for actinic keratosis: results from a case series.

BACKGROUND: In clinical studies, imiquimod 3.75% was shown to detect and treat actinic keratosis (AK) lesions across an entire sun-exposed field such as the full face or balding scalp. The aim of this study was to evaluate imiquimod 3.75% in a real-life clinical setting. METHODS: Ten AK patients applied imiquimod 3.75% to the full face or scalp once-daily in two 2-week treatment cycles separated by a two-week treatment-free interval and were followed-up eight weeks later. Seven patients rated imiquimod 3.75% versus prior treatments (cryotherapy, photodynamic therapy, diclofenac sodium 3%, imiquimod 5%, ingenol mebutate). RESULTS: The median clinical lesion count at baseline was 12.5. This increased to a median Lmax (maximum lesion count during treatment) of 22.5 as imiquimod 3.75% unmasked previously invisible subclinical lesions. At final follow-up, the median lesion count was 0. Local skin reactions such as erythema, scabbing and erosion occurred during each treatment cycle and were easy to manage. All patients considered imiquimod 3.75% easier to apply than prior treatments and 5 reported fewer or similar side effects. CONCLUSIONS: In this cohort, imiquimod 3.75% effectively cleared clinical and subclinical lesions across the entire affected field and was well tolerated.

HLA-C*06:02 Does Not Predispose to Clinical Response Following Long-Term Adalimumab Treatment in Psoriatic Patients: A Retrospective Cohort Study.

BACKGROUND: The genetic basis of predisposition to psoriasis is recognised; however, the response to psoriasis treatment in patients with different genetic predisposition is poorly understood. OBJECTIVE: To analyse the presence of the HLA-C*06:02 polymorphism in psoriatic patients treated with adalimumab. METHODS: Genomic DNA was extracted from whole blood of 122 patients with moderate-to-severe psoriasis treated with adalimumab for 3 years. Genotyping was performed using PCR. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at day 0 and after 1, 3, 6, 12, 24 and 36 months. Logistic regression was used to evaluate the association between dependent variables (including HLA-C*06:02 status) and achievement of PASI 50, 75 and 90. RESULTS: No difference was observed after adalimumab treatment between C*06:02 positive (HLA-C*06:02-POS) patients (n = 46) and C*06:02 negative (HLA-C*06:02-NEG) patients (n = 76) over the 3-year follow-up period in terms of PASI response or time-course when PASI response was achieved. However, a small, but non-statistically significant difference was noted between genotypes for PASI 50 at 1 month (HLA-C*06:02-NEG: 44.7% vs. HLA-C*06:02-POS: 56.5%) and at 3 months (HLA-C*06:02-NEG: 71.1% vs. HLA-C*06:02-POS: 80.4%). Simple logistic regression analysis did not reveal an association between independent variables (including C*06:02 status) and PASI response; however, multivariate regression revealed that gender (females better than males) was associated with achievement of PASI 50 at month 1 (OR 0.34, 95% CI 0.16-0.72, p = 0.005) and of PASI 75 at 3 months (OR 0.36, 95% CI 0.16-0.8, p = 0.012). CONCLUSION: Adalimumab reduced long-term severity in patients with moderate-severe psoriasis, independent of their HLA-C*06:02 status.

Real-life efficacy and safety of ingenol mebutate for the treatment of actinic keratosis of the face and scalp: A single arm retrospective study.

BACKGROUND: The efficacy and safety of ingenol mebutate versus placebo have been proven in four randomized controlled trials (RCTs), although there is a lack of real-life studies corroborating such promises in routine clinical practices. In our study, we sought to describe real-life effectiveness, safety and regimen adherence among patients with multiple AKs on the face treated with ingenol mebutate and evaluate correlates of clinical outcomes in this population. METHODS: We reviewed the clinical charts of adult patients with multiple (≥3) AK grade I and II of the face and scalp, treated with ingenol mebutate from April 2014 to April 2015. All subjects received the medication according to ingenol mebutate standard of care. RESULTS: We enrolled 88 patients during the study period and carried out 122 treatment cycles. The unadjusted lesion clearance rate per treated field was 81.3% and the average local skin reactions score at day 4 was 6.0 ± 2.8 (range: 0-18). CONCLUSIONS: We observed an excellent rate (>99%) of adherence to ingenol mebutate. This was mirrored by the fact that our clinical outcomes broadly confirmed results obtained in RTCs. Our study showed that the efficacy and safety of ingenol mebutate observed in RCTs can be reliably translated in real-world practice.

Treatments of advanced basal cell carcinoma: a review of the literature.

Advanced basal cell carcinoma (aBCC) encompasses locally advanced BCC (laBCC) and metastatic BCC (mBCC), two variants of BCC with a limited prevalence worldwide. Treatment of aBCC is still very challenging for the lack of randomized controlled trials/guidelines and the scarcity of available therapeutic options. Based on current data, surgical procedures and radiotherapy are considered the treatments of choice for aBCC although often associated with substantial morbidity and/or deformity. Alternatively, systemic chemotherapy and electrochemotherapy can be used but standardized treatment schedules and randomized clinical trials are not available for both treatments. In recent years, novel tumor-specific and pathogenesis-based molecules have been developed for the treatment of aBCC. A number of clinical trials have recently demonstrated the efficacy and tolerability of vismodegib, the first novel systemic, anti-Smo target cancer therapy for aBCC. Additional molecules currently investigated in phase I-III clinical trials include other Smo antagonists and itraconazole. The contribution of a multidisciplinary team composed of dermatologists, surgeons, oncologists, pathologists, radiologists and radiotherapists is required to deal with the spectrum of issues that emerge from managing patients affected by aBCC.