Histone Deacetylation Inhibitor Shows Promise for Treating Basal Cell Carcinoma

Histone Deacetylation Inhibitor Shows Promise for Treating Basal Cell Carcinoma
[Source: Justin Pumfrey/Getty Images]

A topical cream that inhibits histone deacetylation is effective at treating basal cell skin cancer, according to results from a Phase II trial.

Basal cell carcinoma (BCC) is the most common cancer around the world and continues to become more common over time. More than 3 million cases are reported in the U.S. each year with an accompanying $4B in healthcare costs.

Although treatments exist, the most common being surgical removal, this can be expensive, time-consuming and unpleasant for patients. Therefore, an effective topical solution would be a valuable medical solution. There are some creams currently available, but they can only be used to target the most superficial type.

“While BCC is not associated with high mortality, surgical excision can be a costly and burdensome treatment, particularly for patients who develop multiple BCC lesions,” said Kavita Sarin, senior author of the Clinical Cancer Research study and an associate professor of dermatology at Stanford University.

Histone deacetylases act by epigenetically modifying gene expression. They were identified as potential anticancer drugs, but human clinical trials of monotherapy for solid tumors have only seen limited success, despite good early results. There are also issues with toxicity when given systemically.

Sarin and co-authors have developed remetinostat in a topical cream formulation to try and avoid toxicity issues and better target skin cancers without needing surgery. It acts by altering histone phosphorylation, suppressing the transcription of the oncogene GLI1, and decreasing tumor size.

For the current study, the team included 30 patients with at least one BCC of 5mm or greater in diameter. Of the group, 90% were non-Hispanic white individuals and 47% had previously had skin cancer. Some of the group had multiple tumors needing treatment and so 49 BCC’s were included in the study in total.

The participants applied the gel to the tumor 3 times a day for 6 weeks and anything remaining was surgically removed and examined after 8 weeks

A total of 33 tumors were included in the analysis. Approximately 70% of the tumors had a response to the therapy and around 55% resolved completely. Across all the tumors tested, application of the gel reduced diameter by 62% and tumor area by 72%.

Importantly, given the adverse effects observed with this kind of therapy when taken systemically, no significant side effects were observed. The most notable was an eczema-like reaction at the application site in some participants.

“While further research is needed, our results suggest that remetinostat could be a safe and promising alternative to surgical treatment of BCC due to the high rate of complete responses we observed,” said Sarin.

“However, if a therapy is to replace surgical treatment, it needs to not only induce a complete response, but also a durable one.” The team now wants to test how long the cream is effective for.

Notably, it seemed to show a good response in patients with nodular as well as superficial BCC, something not seen with other creams.