Systemic BRAF/MEK Inhibitors as a Potential Treatment Option in Metastatic Conjunctival Melanoma

Abstract

Aim: In this review, we outline similarities between conjunctival and skin melanoma as well as the effectiveness of combined BRAF/MEK inhibition in melanoma, and discuss the applicability of these agents in conjunctival melanoma.

Methods: The study provides a PubMed literature review.

Results: Conjunctival melanoma and skin melanoma are genetically and phenotypically related. Both tumors typically harbor BRAF mutations in more than 50% of cases. New targeted therapies in metastatic skin melanoma include selective inhibition of BRAF and MEK. Combined BRAF/MEK inhibition has revolutionized the treatment of metastatic skin melanoma, significantly improving patients' prognoses. While these new substances have been investigated extensively in the treatment of skin melanoma, comparable studies in conjunctival melanoma do not exist owing to the rarity of the malignancy.

Conclusions: The application of combined BRAF/MEK inhibition in metastatic or unresectable conjunctival melanoma shows great potential for improving patients' prognoses. Future studies are needed to investigate the assumed benefit.

Keywords: BRAF inhibitor; Conjunctival melanoma; MEK inhibitor; Metastatic disease; Primary acquired melanosis.

Fig. 1

The MAPK pathway. Following activation of growth factor receptors by their ligands, signal transduction through the Ras-Raf-MEK-MAPK pathway occurs. With the help of Myc and CREB, signals are passed on to the nucleus and lead to transcription of genes that are relevant in proliferation and tumorigenesis. BRAF inhibition tackles signal transduction from Raf to MEK, whereas further downstream, MEK inhibition stops signal transduction from MEK to MAPK, thus counteracting resistance mechanisms that bypass Raf inhibition. L, ligand of growth factor receptor; GF-R, growth factor receptor; BI, BRAF inhibitor; MI, MEK inhibitor; CREB, cAMP response element-binding protein.