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BACKGROUND A better understanding of the molecular pathways that characterize cell growth, apoptosis, angiogenesis, and invasion has provided novel targets in cancer therapy. Epidermal growth factor receptor (EGFR)-mediated signal transduction has been one of the most studied pathways in carcinogenesis. The phosphorylation of EGFR activates multiple biological processes, including apoptosis, differentiation, cellular proliferation, motility, invasion, adhesion, DNA repair, and survival. EGFR is a transmembrane tyrosine kinase receptor involved in the proliferation and survival of cancer cells. EGFR is the first molecular target against which monoclonal antibodies have been developed for cancer therapy.
OBJECTIVE To review the mechanisms underlying the effects of EGFR in nonmelanoma skin cancer (NMSC) and their potential role as targeted therapies in the treatment thereof.
CONCLUSIONS EGFR plays an important role in tumorigenesis of NMSC, especially metastatic squamous cell carcinoma, via mechanisms similar to those of other visceral tumors. Pharmacologic inhibitors of EGFR pathway of tumor production may offer an effective therapeutic strategy to block tumor growth.
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Background The role of growth hormone, insulin, and insulin-like growth factor-1 (IGF-1) in the development of acne is incompletely understood.
Objective To study the effect of the absence of IGF-1 and its pharmacologic replacement on the occurrence of acne vulgaris.
Patients and Methods Laron syndrome (LS) is characterized by congenital IGF-1 deficiency. The study group consisted of 21 patients with classical LS, who underwent puberty: 13 (8 male, 5 female) untreated and under regular follow-up until age 2048 years; and 8 (2 male, 6 female) treated with IGF-1 (70–200 lg/kg/day), including 6 adults (2 male, treated at age 14.5–29 years and 4 female, treated at age 30–37 years) and 2 adolescents (2 female, treated at age 3.5–16 years). The medical files were reviewed for occurrence of acne and the corresponding sex hormone levels, and the findings were compared between the treated and untreated patients.
Results Puberty was delayed in all untreated patients. Only one patient had slight acne at age 22 years, when he reached full puberty. Among the 2 IGF-1 treated male patients, none acquired acne. Among the 6 treated female patients, 3 had signs of hyperandrogenism (oligo-amenorrhea) and acne during IGF-1 over-dosage. On reduction of the IGF-1 dose (to 50 lg/kg/day) or cessation of treatment, the acne disappeared in all 3 patients.
Conclusion This study demonstrates for the first time that serum IGF-1 deficiency prevents the occurrence of acne. The findings suggest that an interaction between IGF-1 and androgens is necessary for the development of acne.
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Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis of these first- and second-generation TKIs’ cutaneous side effects, and approaches to their treatment. The wide range of adverse effects clarifies the difficulty in designing a truly antitumoral TKI.
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Cases of lymphoma or cutaneous cancer have been observed following use of topical calcineurin inhibitors (TCIs), but it is unclear whether TCI use increases cancer risk. We used published literature to assess the extent to which atopic dermatitis (AD) or TCI use is associated with lymphoma, melanoma, basal cell carcinoma and squamous cell carcinoma. We searched the literature and summarized the results of all studies that provided data on the absolute or relative frequency of any malignancy among patients with AD or eczema or among patients using TCIs. The relative risk for all lymphoma in broad populations of AD or eczema ranged from 0Æ7 to 1Æ8. Available data on lymphoma following TCI use were inconsistent and insufficient to draw a conclusion about the causal role of TCIs. We found no evidence indicating that melanoma or nonmelanoma skin cancer is associated with TCI use. A bias analysis showed that cutaneous T-cell lymphomas initially misdiagnosed and treated as AD would lead to overestimation of the association between TCI use and lymphoma. However, there are only sparse data on specific malignancies among TCI-treated patients. The short duration of typical TCI exposure hinders conclusions about longer exposure. There is insufficient evidence in the epidemiological literature to infer whether TCIs do or do not cause malignancy.
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