Aleksandar Sekulic, MD, PhD, chief resident associate, Dermatology, Clinician Investigator Training Program, Mayo Clinic, discusses the rationale for molecular testing in patients with advanced melanoma.

There are various molecular tests that can be viewed as an adjunct to diagnosis and prognosis of melanoma. It is routine to conduct molecular testing for BRAF mutation to help oncologists determine if patients will respond to BRAF inhibitors. This type of molecular testing should always be implemented, Sekulic explains.

In a broader sense, molecular testing aims to find other targets that may not have defined therapies associated with them, Sekulic says. This challenge has led researchers to form the Melanoma Dream Team for the Stand Up to Cancer trial. This will determine if patients can be treated with specific therapies based on molecular test findings and, if so, what the best practices would be used to accomplish this. Within this trial, researchers are using whole-exome sequencing and long insert whole genome sequencing.

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Dr. Sekulic on Molecular Testing in Advanced Melanoma

Aleksandar Sekulic, MD, PhD, Assistant Professor of Dermatology, Mayo Clinic, Scottsdale, AZ, discusses the administration of the oral hedgehog pathway inhibitor vismodegib (Erivedge) for the treatment and prevention of basal-cell carcinoma (BCC) in patients with basal-cell nevus syndrome, a rare disorder also known as Gorlin syndrome.

A phase II trial randomized 41 patients with basal-cell nevus syndrome in a 2:1 ratio to received vismodegib or placebo for 18 months. In the trial, patients treated with vismodegib demonstrated fewer new BCCs and a reduction in the size of existing BCCs when compared to placebo.

Sekulic believes that vismodegib holds the potential to be a game changer by offering a significant clinical benefit for patients with this rare syndrome.

Aleksandar Sekulic, MD, PhD, from the Mayo Clinic, Scottsdale, AZ, discusses the administration of vismodegib for the treatment and prevention of basal-cell carcinoma in patients with basal-cell nevus syndrome.

Dr. Sekulic on Vismodegib for Basal-Cell Nevus Syndrome

Aleksandar Sekulic, MD, PhD, Assistant Professor of Dermatology, Mayo Clinic, Scottsdale, AZ, discusses the Hedgehog pathway inhibitor vismodegib (Erivedge), which is approved for patients with basal cell carcinoma (BCC) and is under investigation in multiple other tumor types.

Vismodegib is an active inhibitor of the smoothened receptor, which is a key link in the Hedgehog signaling pathway. Overall, smoothened is implicated in greater than 90% of patients with BCC that have an activated Hedgehog pathway. Sekulic believes this makes it a successful target in a broad spectrum of patients.

In addition to vismodegib's activity in malignant cells it will also bind to smoothened in normal small compartment cells, such as hair follicles and taste buds. This inhibition in the noncancerous cells explains some of the adverse events of the drug, which includes altered taste and hair loss.

Dr. Aleksandar Sekulic, from the Mayo Clinic in Arizona, on the Hedgehog Pathway Inhibitor Vismodegib for Basal Cell Carcinoma.

Aleksandar Sekulic, MD, PhD

Articles

Dr. Sekulic on Molecular Testing in Advanced Melanoma

Dr. Sekulic on Vismodegib for Basal-Cell Nevus Syndrome

Dr. Sekulic on the Hedgehog Pathway Inhibitor Vismodegib