Squamous Cell Carcinoma as a Complication of Long-Term Hydroxyurea Treatment

Hydroxyurea therapy is commonly used in the treatment of patients suffering from myeloproliferative diseases, such as polycythemia vera. It is supported by evidence that this type of therapy can generate mild skin lesions like leg ulcers, erythema, and hyperpigmentation. There are also some studies that show an increased risk of development of nonmelanoma skin cancers. We report a 56-year-old man with a 13-year history of polycythemia vera, treated chronically with hydroxyurea. In April 2020, the patient presented a skin lesion on the forehead, skin horn on the left forearm, and hyperkeratosis on the rims of both ears. In the patient’s history, in October 2019, complete excision of the skin lesion in the central area of the forehead was performed. After 4 months, a new skin lesion appeared at the same area of the forehead, which in May 2020 after resection in the histopathological examination was diagnosed as recurrence of squamous cell carcinoma. The aim of the case is to draw the clinicians’ attention to the increased risk of squamous cell carcinoma and basal cell carcinoma in patients treated with hydroxyurea. Increased vigilance would make it possible to recognize them earlier, and thus potentially reduce the undesirable effects associated with the delayed radical treatment of these skin cancers. Randomized clinical trials assessing the potential benefits of oral retinoids for chemoprevention of nonmelanoma skin cancers in the hydroxyurea-treated population should also be considered.

Hydrochlorothiazide Use and Risk of Nonmelanoma Skin Cancers: A Biological Plausibility Study

Recent studies reported the association between increased risk of nonmelanoma skin cancers (NMSCs) and the use of hydrochlorothiazide (HCTZ), one of the most commonly prescribed diuretic, antihypertensive drug, over the world. Although HCTZ is known to be photosensitizing, the mechanisms involved in its potential prophotocarcinogenic effects remain unclear. Under acute exposure, therapeutically relevant concentrations of HCTZ (70, 140, and 370 ng/mL) amplified UVA-induced double-strand breaks, oxidative DNA, and protein damage in HaCaT human keratinocytes, and this effect was associated to a defective activity of the DNA repair enzyme, OGG1. Oxidative damage to DNA, but not that to proteins, was reversible within few hours. After chronic, combined exposure to HCTZ (70 ng/mL) and UVA (10 J/cm2), for 9 weeks, keratinocytes acquired a dysplastic-like phenotype characterized by a multilayered morphology and alterations in cell size, shape, and contacts. At the ultrastructural level, several atypical and enlarged nuclei and evident nucleoli were also observed. These transformed keratinocytes were apoptosis resistant, exhibited enhanced clonogenicity capacity, increased DNA damage and inflammation, defective DNA repair ability, and increased expression of the oncogene ΔNp63α and intranuclear β-catenin accumulation (a hallmark of Wnt pathway activation), compared to those treated with UVA alone. None of these molecular, morphological, or functional effects were observed in cells treated with HCTZ alone. All these features resemble in part those of preneoplastic lesions and NMSCs and provide evidence of a biological plausibility for the association among exposure to UVA, use of HCTZ, and increased risk of NMSCs. These results are of translational relevance since we used environmentally relevant UVA doses and tested HCTZ at concentrations that reflect the plasma levels of doses used in clinical practice. This study also highlights that drug safety data should be followed by experimental evaluations to clarify the mechanistic aspects of adverse events.

Rapid development of multiple nonmelanoma skin cancers secondary to ruxolitinib: a case report

<p class="abstract">Janus kinase (JAK) inhibitors are immunosuppressive medications that function by deactivating the JAK-STAT pathway causing inhibition of cellular growth. Ruxolitinib is a JAK inhibitor that is commonly used to treat disease processes such as myelofibrosis, polycythemia vera and graft versus host disease, with some evidence of benefit with prostate cancer as well. Side effects of ruxolitinib include increased risk of infection, pancytopenia, cardiovascular disease and malignancy relating to the medication’s immunosuppressive effects. Here we reported a 69-year-old male with prostate cancer being treated with ruxolitinib who developed multiple nonmelanoma skin cancers over a 13-month period.</p>

Therapeutic Application of Melatonin in the Treatment of Melanoma: A Review

Melanoma is an aggressive type of skin cancer, which is responsible for more deaths than nonmelanoma skin cancers. Therapeutic strategies include targeted therapy, biochemotherapy, immunotherapy, photodynamic therapy, chemotherapy, and surgical resection. Depending on the clinical stage, single or combination therapy may be used to prevent and treat cancer. Due to resistance development during treatment courses, the efficacy of mentioned therapies can be reduced. In addition to resistance, these treatments have serious side effects for melanoma patients. According to available reports, melatonin, a pineal indolamine with a wide spectrum of biological potentials, has anticancer features. Furthermore, melatonin could protect against chemotherapy- and radiation-induced adverse events and can sensitize cancer cells to therapy. The present review discusses the therapeutic application of melatonin in the treatment of melanoma. This review was carried out in PubMed, Web of Science, and Scopus databases comprising the date of publication period from January 1976 to March 2021.