TargetingBRAFMutations in High-Grade Neuroendocrine Carcinoma of the Colon

• DOI: 10.6004/jnccn.2018.7043
• Publication Date: 2018-09-04T18:45:21Z
• Authors: Jarred Burkart; Dwight Owen; Manisha H. Shah; Sherif R. Z. Abde...; Sameek Roychowdhury; Robert Wesolowski; Sigurdis Haraldsd...; Julie W. Reeser; Eric Samorodnitsky; Amy Smith; Bhavana Konda
• Keywords: Targeted Therapy; V600E

Mutations in the RAS/RAF/MEK/ERK pathway leading to constitutive activation and uncontrolled cellular growth have been identified various human malignancies, making this a target for potential therapeutics. The activating BRAFV600E mutation is one well-characterized oncogenic that has described targeted with clinical success including melanoma hairy cell leukemia. Although BRAF-directed treatments yielded benefit subset of tumor types, such as melanoma, thyroid cancer, lung BRAF inhibition fails confer colon cancer. Identification patients whom may produce clinically meaningful outcomes imperative. incidence mutations neuroendocrine carcinoma (NEC) estimated be 5% 10%. A recent case series demonstrated targeting metastatic high-grade rectal NECs. Combination MEK known yield improved compared alone melanoma. This report presents 2 colorectal NECs who had different responses treatment combined BRAF/MEK after experiencing disease progression through first-line platinum-based chemotherapy. One patient experienced an excellent initial response therapy before ultimately progression, other initially stable eventually progression. These cases highlight complicated role play gastrointestinal NECs, need further research identify not only from therapies but also strategies avoid development resistance.