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The first class histone deacetylase inhibitor gel is promising for the treatment of patients with basal cell carcinoma

Remethinostat, a topical cream and a first-in-class inhibitor of histone deacetylation, Clinical cancer research..

Basal cell carcinoma (BCC) is the most common form of skin cancer and is usually Surgical excisionKavita Sarin, MD, Ph.D., Senior Author of the Study and Associate Professor of Dermatology, Stanford University. Explained.

“BCC is not associated with high mortality, but surgical resection can be a costly and costly treatment, especially for patients who develop multiple BCC lesions,” she said.

A potential alternative strategy is to treat BCC with a topical cream. However, existing topical treatments for BCC are only effective against superficial subtypes of BCC, emphasizing the need for more widely applicable topical treatments, Sarin explained.

Sarin et al. Previously identified histone deacetylase (HDAC) inhibition as a promising therapeutic approach to BCC. In their latest study, a phase II clinical trial, Sarin et al. Evaluated the safety and efficacy of the HDAC inhibitor remethinostat in adult patients with BCC. Unlike systemic HDAC inhibitors, which may be associated with a variety of toxicities, remethinostats are designed to be ineffective when absorbed beyond the skin and localize their activity to skin lesions. can do.

Thirty patients were enrolled in this study, and each patient had at least one BCC with a diameter of 5 mm or more at the time of diagnosis. 90% and almost half of the patients identified as non-Hispanic Caucasians had a history of skin cancer. Eight patients had multiple eligible tumors, resulting in a total of 49 tumors in this study. Tumors were found in both sun-exposed and non-sun-exposed parts of the body, most with nodular or superficial histology.

Participants applied Remethinostat gel to the tumor three times daily for 6 weeks. Eight weeks later, the remaining tumor was surgically resected and histologically examined.

Of the 33 tumors included in the final analysis, 69.7% responded to topical treatment with 17 complete and 6 partial responses. On average, tumor diameter decreased by 62.3%, tumor Area decreased by 71.5 percent.

Responses were observed with multiple BCC subtypes: 100% response rate (5 complete responses, 1 partial response) in 6 superficial BCC tumors, 68.2% response in 22 nodular BCCs Rate (10 complete responses, 5 partial responses)), and 66.7 percent of 3 invasive BCCs (2 complete responses). No response was observed in the two tumors of the micronodular subtype.

No systemic or serious adverse events have been reported. The most reported adverse event was an eczema-like skin reaction at the site of application of Remethinostat.

“While further research is needed, our results suggest that remethinostat may be a safe and promising alternative to surgical treatment of BCC due to the high rate of complete response we have observed. “I will,” said Sarin. “But if treatment replaces surgical treatment, it must not only elicit a complete response, but also a durable response,” says Sarin in future trials. , We plan to investigate the lifetime of the reaction to remethinostat.

“Our study also showed the clinical effect of remethinostat on one of the more common BCC subtypes, nodular BCC,” Sarin added. “The ideal treatment for BCC should treat both nodular and superficial BCC, and ideally other subtypes as well.”

Research limitations include the small sample size, its single-arm design, and lack of durability data. This study was supported by Medivir AB, Damon Runyon Foundation, National Cancer Institute, American Skin Association Medical Student Grant, and Stanford Medical Scholars. Sarin does not declare a conflict of interest.


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For more information:
Clinical cancer research (2021). DOI: 10.1158 / 1078-0432.CCR-21-0560

Quote: First-in-class histone deacetylase inhibitor gel was obtained from https://medicalxpress.com/news/2021-08-first-in- on August 6, 2021 for basal cell carcinoma (2021, 2021). It is promising for the treatment of patients (August 6). Class-Histone-Deacetylase-Inhibitor-gel.html

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The first class histone deacetylase inhibitor gel is promising for the treatment of patients with basal cell carcinoma

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