Advanced Basal Cell Cancer: Concise Review of Molecular Characteristics and Novel Targeted and Immune Therapeutics

M. Nikanjam; P. R. Cohen; S. Kato; J. K. Sicklick; R. Kurzrock

Disclosures

Ann Oncol. 2018;29(11):2192-2199. 

In This Article

Discussion

While BCC is a common malignancy, metastatic BCC is extremely rare and the majority of these tumors are dependent on the Hedgehog signaling pathway for growth and proliferation. Hedgehog inhibitors, including vismodegib and sonidegib, are approved by the EMA and the FDA, and offer therapeutic improvements over traditional cytotoxic chemotherapy; however, resistance still develops, often within months. Response rates to hedgehog inhibitors are likely lower in metastatic BCC due to reduced rates of PTCH1 alterations. Indeed, metastatic basal carcinoma may represent a subgroup of cutaneous BCC with specific phenotypic and genomic changes, which will necessitate novel treatment approaches. A plethora of other targets have been studied in metastatic and advanced BCC tumors and there are anecdotal reports demonstrating that individualizing treatments designed in order to target these alterations can be effective. For instance, a patient with a VEGFR2alteration achieved a CR after being given the VEGFR inhibitor pazopanib. Furthermore, a subset of patients have high TMB and/or PD-L1 amplification, features that predict response to checkpoint blockade immunotherapy.[6,55,56,67] A better understanding of the genomic portfolio of metastatic and advanced BCC should assist in developing therapeutic approaches to improve responses and overcome resistance.

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