Anti-MAPK Targeted Therapy for Ameloblastoma: Case Report with a Systematic Review

Abstract

Ameloblastoma, a benign yet aggressive odontogenic tumor known for its recurrence and the severe morbidity from radical surgeries, may benefit from advancements in targeted therapy. We present a case of a 15-year-old girl with ameloblastoma successfully treated with targeted therapy and review the literature with this question: Is anti-MAPK targeted therapy safe and effective for treating ameloblastoma? This systematic review was registered in PROSPERO, adhered to PRISMA guidelines, and searched multiple databases up to December 2023, identifying 13 relevant studies out of 647 records, covering 23 patients treated with MAPK inhibitor therapies. The results were promising as nearly all patients showed a positive treatment response, with four achieving complete radiological remission and others showing substantial reductions in primary, recurrent, and metastatic ameloblastoma sizes. Side effects were mostly mild to moderate. This study presents anti-MAPK therapy as a significant shift from invasive surgical treatments, potentially enhancing life quality and clinical outcomes by offering a less invasive yet effective treatment alternative. This approach could signify a breakthrough in managing this challenging tumor, emphasizing the need for further research into molecular-targeted therapies.

Keywords: adverse effect; ameloblastoma; anti-BRAF/MEK; effectiveness; targeted therapy.

Figure 1

Different radiographic images before and after treatment, showing the evolution of the lesion. (A): Panoramic X-rays before treatment with a cystic lesion, unerupted second molar, and interrupted cranial cortical. (B): A 3D reconstruction of a CBCT pre- and post-treatment with complete ossification of the interrupted cortical border of the mandible. (C): CBCT in a modified sagittal view pre- and post-treatment. To note, the complete eruption and occlusion of the second molar.

Figure 2

Different histological analysis. (A): Histological analysis of the initial biopsy shows epithelial strands of basal cells with palisaded and hyperchromatic nuclei, and centrally located stellate reticulum-like cells with acanthomatous changes (H&E, 20×). (B): BRAF immunostain shows moderate cytoplasmic positivity in tumoral cells (40×). (C,D): Enucleation after anti-BRAF therapy shows residual tumor admixed with inflammatory cells, including lymphocytes and giant multinucleated cells (left), and surrounded by large areas of fibrosis (right) (H&E, 20×).

Figure 3

Moher D. et al. [25] for the Preferred reporting guideline in systematic reviews and meta-analysis (PRISMA) flow diagram.

Figure 4

Risk of Bias assessment of the included studies [31,32,33,34,35,36,37,38,39,40,41,42,43]. Domains of the Risk of Bias Assessment Tool. (1) Were the patient’s demographic characteristics clearly described? (2) Was the patient’s history clearly described and presented as a timeline? (3) Was the current clinical condition of the patient on presentation clearly described? (4) Were diagnostic tests or assessment methods and the results clearly described? (5) Was the intervention(s) or treatment procedure(s) clearly described? (6) Was the post-intervention clinical condition clearly described? (7) Were adverse events (harms) or unanticipated events identified and described? (8) Does the case report provide takeaway lessons? (Y) Yes, (N) No, (U) Unclear or (N/A) Not/Applicable.

Figure 5

Schema of the mitogen-activated protein kinase (MAPK) pathway from the outer membrane to the nucleus. On the (left), its normal activation by Extracellular signal-regulated Kinases called ERK (FGF, EGF, etc.) binding to receptor tyrosine kinase RTK (FGFR, EGFR, etc.) and thus activating the cascade signaling through RAS–RAF–MEK–ERK, finally regulating cellular biological function. Without extracellular signals activating the phosphorylation of RAS, the pathway is switched off. Few examples of targeted therapies. On the (right), the different mutated genes of the pathway cause its constitutive activation without external stimuli, leading to cell proliferation. Mutations in the RAS gene (NRAS, KRAS, and HRAS), in the FGFR gene (FGFR2), and in the RAF gene (BRAF) are the most common.