In this clinically rich episode, host Dr. Ted Lain sits down with board-certified dermatologist and global skin cancer expert Dr. Todd Schlesinger — AAD Board of Directors member, Mohs surgeon, clinical assistant professor at George Washington University School of Medicine, and medical director of the Clinical Research Center of the Carolinas — for a deep dive into systemic and targeted therapies for non-melanoma skin cancer (NMSC).

The doctors begin with a thorough breakdown of the hedgehog signaling pathway (PATCHED, Smoothened, GLI-1 transcription) and how mutations in this pathway drive basal cell carcinoma (BCC) growth. They compare the two FDA-approved hedgehog pathway inhibitors (HHIs) — vismodegib (Erivedge) and sonidegib (Odomzo) — covering their mechanisms of action, volume of distribution differences (16–18L vs. ~9,000L), indications for locally advanced and metastatic BCC, how to define "locally advanced," and complete vs. partial response rates. Dosing strategies are addressed in detail, including alternate-day dosing and treatment breaks backed by the MIKIE study and STEVIE safety study. For managing the most common adverse events — muscle cramps, dysgeusia, weight loss, and fatigue — Dr. Schlesinger shares his clinical protocol using L-carnitine supplementation (1,500–2,000mg liquid, started 2–4 weeks before therapy) along with calcium and CoQ10.

The conversation then moves to PD-1 and PD-L1 checkpoint inhibitors for locally advanced and metastatic cutaneous squamous cell carcinoma (cSCC) and BCC, covering cemiplimab (Libtayo), pembrolizumab (Keytruda), and nivolumab (Opdivo). The hosts explain the immune checkpoint mechanism using a memorable analogy, discuss how UV exposure upregulates PD-1 on tumor cells, and explore the practical realities of dermatologists prescribing infusion-based immunotherapy — including multidisciplinary care team logistics, buy-and-bill considerations, and when to partner with oncology.

The episode closes with an exciting look at the pipeline: intralesional therapies for nodular and superficial BCC from companies including Verica, iViva, PHIO, and Feldan, red light PDT for superficial BCC nearing FDA approval, and the broader question of where these drugs fit as neoadjuvant, adjuvant, or primary therapies — and what complete response benchmarks (80–95%) dermatologists should expect before adopting non-surgical primary options.

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DISCLAIMER: This podcast is not intended to provide diagnosis, treatment, or medical advice. Content provided in this podcast is for educational purposes only. Please consult with a physician regarding any health-related diagnosis or treatment.