clobetasol and Neoplasms

X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis proteins family of caspase inhibitors that selectively binds and inhibits caspases-3, -7 and -9, but not caspase-8. As such, XIAP blocks a substantial portion of the apoptosis pathway and is an attractive target for novel therapeutic agents for the treatment of malignancy. Antisense oligonucleotides directed against XIAP are effective in vitro and are currently being evaluated in clinical trials. Small molecule XIAP inhibitors that target the baculovirus IAP repeat (BIR) 2 or BIR 3 domain are in preclinical development and are advancing toward the clinic. This review will discuss the progress being made in developing antisense and small-molecule XIAP inhibitors.

Topics: Apoptosis; Benzoquinones; Caspase Inhibitors; Clobetasol; Humans; Neoplasms; Oligonucleotides, Antisense; Protein Structure, Tertiary; Ubiquitin-Protein Ligases; X-Linked Inhibitor of Apoptosis Protein

To our knowledge, there have been no previous reports of eruptive keratoacanthomas (KAs) in patients receiving pembrolizumab.. To report the cases of 3 consecutive patients with pembrolizumab-induced eruptive KAs and their management.. Case report study of 3 patients from 2 centers with pembrolizumab-treated cancer who all developed eruptive KAs.. All 3 patients had AK treatment with clobetasol ointment and intralesional triamcinolone; 2 patients also underwent open superficial cryosurgery.. Three consecutive patients with cancer, 2 men and 1 woman (median age, 83 years; range 77-91 years), experienced pembrolizumab-associated eruptive KAs. All patients presented with a sudden onset of multiple lesions on sun-exposed areas of their extremities after a median of 13 months (range, 4-18 months) of pembrolizumab therapy. On lesional biopsy, a lichenoid infiltrate was observed in the underlying dermis, predominantly composed of CD3+ T cells, scattered CD20+ B cells, and relatively few PD-1+ (programmed cell death 1-positive) T cells, an immunophenotypic pattern also observed in other cases of anti-PD-1-induced lichenoid dermatitis. Patients were treated with clobetasol ointment and intralesional triamcinolone, alone or in combination with open superficial cryosurgery. All KAs resolved in all patients, and no new lesions occurred during close follow-up. Pembrolizumab treatment was continued without disruption in all 3 cases, and all patients had complete responses of their primary cancers.. Pembrolizumab is used in advanced melanoma, advanced non-small-cell lung cancer, and in head and neck cancer. A variety of dermatologic immune-related adverse events including maculopapular eruption, lichenoid reactions, pruritus, and vitiligo have been described. This case series demonstrates that pembrolizumab therapy may also be associated with eruptive KAs with characteristic dermal inflammation, which improved with corticosteroid treatment (topical and intralesional) alone or in combination with cryosurgery, allowing patients to continue therapy with pembrolizumab.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Biopsy; Clobetasol; Cryosurgery; Female; Follow-Up Studies; Glucocorticoids; Humans; Keratoacanthoma; Male; Neoplasms; Time Factors; Triamcinolone