Effectiveness of Molecular-Targeted Chemotherapy in Ameloblastomas

Abstract

Ameloblastoma is a benign, locally aggressive neoplasm that needs extensive surgical resection. The goal of this article is to obtain an in-depth review of benign ameloblastomas to determine the available level of evidence and the possible benefit of targeted therapeutics for the treatment of ameloblastoma and BRAF V600E mutation in ameloblastoma. An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, EBSCO, and Web of Science for eligible studies published between 1975 and 2021. The systematic review is registered with INPLASY (INPLASY202260018). The review included 2 case series and 17 case reports. The histopathological type, anatomic location, expression of BRAF mutation, additional mutations, and molecular-targeted therapies of the 19 reviewed articles were summarized and tabulated. Interestingly, the majority of the primary site of ameloblastoma was located in the mandible (80.9%) compared to the maxilla (17%). The tumour size was reported in nine of the included studies. Most of the included studies in the review exhibited ameloblastoma with BRAF V600E mutations and responded to molecular-targeted therapies. Molecular therapies employing BRAF and/or MEK inhibitors in ameloblastoma with BRAF V600E mutations proved to be an appropriate treatment based on the limited available evidence. It is essential further to deepen our understanding at the clinical and molecular level to enhance the precision of management of ameloblastoma.

LRP5, SLC6A3, and SOX10 Expression in Conventional Ameloblastoma

“…When mutations in BRAFV600E and SMO are observed, the possibility of using specific inhibitors for chemotherapy opens. The joint use of dabrafenib/trametinib or only dabrafenib has led to a remarkable reduction in tumor volume [ 41 , 42 , 43 ].…”

“…The DrugBank analysis confirmed the use of vorinostat for the treatment of neoplasms including oral, head, and neck cancer; however, no evidence specifically for ameloblastoma has been reported yet. Molecular target treatments are still limited, and the evidence reported has focused on BRAF and/or MEK inhibitors [ 42 , 43 ]. Both parthenolide and vorinostat have been shown to be effective in combined use with other chemotherapeutic drugs, as they can help reduce the associated toxicity, as well as chemoresistance, thus amplifying the therapeutic effect of chemotherapy, in cholangiocarcinoma and T-cell acute lymphoblastic leukemia cell lines [ 50 , 51 ].…”

Does BRAF mutation status and related clinicopathological factors affect the recurrence rate of ameloblastoma? A systematic review, meta‐analysis and metaregression

“…However, some studies have reported a higher recurrence rate of ameloblastoma in patients with BRAFv600e mutations who underwent surgical treatment, and literature reviews have postulated using BRAF inhibitor therapy in patients with BRAFv600 + ameloblastoma 15 . Therefore, it is plausible that patients with BRAFv600e positive ( BRAFv600e +) ameloblastoma may benefit from escalated single‐modality surgical management 16 . Against this background, this systematic review investigated whether the BRAF‐v600e mutation is associated with an increased risk of ameloblastoma recurrence.…”

“…15 Therefore, it is plausible that patients with BRAFv600e positive (BRAFv600e+) ameloblastoma may benefit from escalated single-modality surgical management. 16 Against this background, this systematic review investigated whether the BRAF-v600e mutation is associated with an increased risk of ameloblastoma recurrence. Additionally, we examined if clinicopathological variables of ameloblastoma have any impact on the recurrence in both BRAFv600e+ and BRAFv600eÀ ameloblastoma groups.…”