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The Role of Actin in Muscle Spasms in a Case Series of Patients with Advanced Basal Cell Carcinoma Treated with a Hedgehog Pathway Inhibitor

Basal cell carcinoma (BCC) is the most common cancer globally, with the incidence increasing worldwide by approximately 1% annually. While most cases of BCC can be treated surgically, advanced BCC often poses treatment challenges for patients unsuitable for, or refractory to, radiotherapy and surgery. Since the majority of cases of BCC demonstrate Hedgehog signaling hyperactivation, Hedgehog pathway inhibitors provide durable treatment options and improved clinical outcomes for patients with advanced BCC. One of the most common adverse events seen in patients taking Hedgehog inhibitors includes muscle spasms, which are hypothesized to occur because of calcium influx into the muscle cells. Here we present a case series of patients with muscle spasms during treatment with sonidegib and propose an alternate etiology related to increased actin expression.

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S2151 Sonidegib (NVP-LDE225) Sonidegib (Erismodegib, NVP-LDE225) is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human) in cell-free assays, respectively. Phase 3. (44) (3)

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