Novel RNA interference approach shows safety, efficacy in cutaneous SCC

A novel therapeutic approach targeting transforming growth factor-B1 and cyclooxygenase-2 demonstrated safety and efficacy in a small cohort of patients with cutaneous in situ squamous cell carcinoma, according to study findings.

“Overexpressed transforming growth factor-beta1 (TGF-B1) and cyclooxygenase-2 (COX-2) are strongly associated with [squamous cell carcinoma (SCC)] development,” Mark Nestor, MD, PhD, of the department of dermatology and cutaneous surgery at the University of Miami Miller School of Medicine, and colleagues wrote.

They added that therapeutic approaches using these targets have shown efficacy not only in SCC, but also in nonmelanoma skin cancer.

“The use of RNA interference (RNAi) therapeutics to silence TGF-B1 and COX-2 in NMSC deserves attention as a noninvasive alternative to conventional surgery,” the researchers wrote.

The group conducted a single-center, open label dose escalation study of various doses of TGF-B1/COX-2 combined with histidine-lysine polypeptide (siRNA/HKP) nanoparticle silencing therapeutic.

Patients received weekly injections for up to 6 weeks. The lowest dose was 10 µg per treatment, while others received 20 µg, 30 µg, 60 µg and 120 µg per treatment.

The analysis included 25 participants (mean age, 67 years; standard deviation, 10 years; 52% men).

Complete histological clearance served as the primary outcome measure. Secondary endpoints included the incidence and severity of treatment-emergent adverse events, serious adverse events and the incidence and severity of local skin response.

Results showed that 19 patients, or 76% of the study population, reached the primary endpoint.

The clearance rate for the 30 µg per treatment group was 80%, while those in the 60 µg group had a 100% clearance rate.

Safety data showed that five patients experienced seven adverse events. No severe or serious adverse events were observed. Moreover, the events that were reported were not associated with the treatment. These events did not lead to treatment discontinuation or study interruption.

The researchers noted that local skin response was “none to minimal” in the majority of the cohort. Improvement was seen at all dosing levels except 120 µg per treatment.

“Intralesional TGF-B1/COX-2 siRNA/HKP nanoparticle therapeutic injections appear to be noninvasive, safe and efficacious in treating cutaneous in situ squamous cell carcinoma,” the researchers concluded. “The recommended doses for future study of the investigational product are 30 µg/treatment and 60 µg/treatment.”