Treatment of a BRAF V600E Positive Ameloblastoma in a Pediatric Patient with MEK Inhibitor Monotherapy

Daws, Steven; Chaiyasate, Kongkrit; Lehal, Arshi

doi:10.1177/27325016211005126

Cited by 7 publications

(13 citation statements)

References 31 publications

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“…In addition they cited their institutional preference for the use of the MEK inhibitor and a greater comfort in the side effect profile. After progression of disease on this regimen, the patient was successfully treated with surgery 24 …”

Section: Discussionmentioning

confidence: 99%

“…Tan et al report on a case of unresectable, recurrent ameloblastoma treated with neoadjuvant dabrafenib with a strong clinical response that reduced the tumor size enough to make it resectable 27 . Hirschorn and Dawes et al describe its use in the neoadjuvant setting for unicystic ameloblastoma allowing them to reduce the magnitude and morbidity of surgery in the pediatric population 19,24 …”

Section: Discussionmentioning

confidence: 99%

“…The identification of these potential targets for treatment is well documented 12,16–18 . In addition, the use of precision medicine for complex ameloblastoma shows demonstrable treatment response 15,19–29 …”

Section: Introductionmentioning

confidence: 99%

“…12,[16][17][18] In addition, the use of precision medicine for complex ameloblastoma shows demonstrable treatment response. 15,[19][20][21][22][23][24][25][26][27][28][29] Our aim is to elucidate the most common genomic alterations found in complex ameloblastoma through comprehensive genetic profiling (CGP). In addition, we examine treatment response to precision medicine in ameloblastoma through a systematic review of currently published cases.…”

Section: Introductionmentioning

confidence: 99%

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Genomic profiling and precision medicine in complex ameloblastoma

Gates

Clark²,

Cherkas

et al. 2023

Head & Neck

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Background: Ameloblastoma may present a significant treatment challenge in the locally advanced, recurrent and metastatic setting. Comprehensive genomic profiling (CGP) can identify targetable genomic alterations to aid in treatment. Methods: Ameloblastoma samples were sequenced using hybrid-capture based sequencing. A systematic literature review was performed to examine outcomes in studies employing targeted treatment in ameloblastoma. Results:We reviewed 14 cases of Ameloblastoma using CGP. There were six patients with activating BRAF mutations, five with PIK3CA, five with SMO, four with FGFR2, one with EGFR, and one with ROS1. All cases were MSI stable and the median TMB was 2.5 mutations/Mb. A separate literature review of clinical outcomes in ameloblastoma showed a predominance of at least partial response to targeted treatment (7/12 cases). Conclusion:CGP is helpful in identifying specific driver mutations in patients with complex ameloblastoma. Targeted treatment has been employed with success in achieving treatment response.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genomic profiling and precision medicine in complex ameloblastoma

Gates

Clark²,

Cherkas

et al. 2023

Head & Neck

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“…However, there is only one case report that showed no response to using trametinib in a 13year-old female with mutated BRAF ameloblastoma. Further studies on the efficacy and appropriate dosage for trametinib for BRAF mutated ameloblastoma were then suggested (Daws et al, 2021) (Table 3). Although treatment of ameloblastoma with BRAF and MEK inhibitors and TKI have been investigated, using ERK inhibitors for treatment of ameloblastoma have never been explored.…”

Section: Targeted Therapies On Ameloblastomamentioning

confidence: 99%

Gene Mutations in the FGF-MAPK Signaling Pathway and Targeted Therapy in Ameloblastoma

Boonsong¹,

Laosuwan²,

Kitkumthorn³

et al. 2022

CMUJNS

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Ameloblastoma is one of the most common odontogenic tumors in Asia. In the past decade, many studies have shown gene mutations in the mitogen-activated protein kinase (MAPK) signaling pathway, especially on an extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Mutations of fibroblast growth factor receptor 2 (FGFR2), rat sarcoma virus (RAS), and B-rapidly accelerated fibrosarcoma (BRAF) are able to cause a continuous activation of the ERK1/2 signaling pathway, hence uncontrolled tumor cell proliferation. Due to the ERK1/2 signaling pathway role in cell growth and cell survival, upregulation of this pathway can cause approximately one-third of human tumors including ameloblastoma. After the discovery of gene mutations in several cancers, many inhibitors have been designed to target these mutations. We, here, reviewed the alteration of the FGF-MAPK signaling pathway in ameloblastoma and targeted treatment used as an adjuvant or neoadjuvant therapy for ameloblastoma especially in cases where wide surgical resection is needed. Keywords: Genetic, Growth factor, Mutation, Targeted therapy

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Histopathologic and Molecular Insights Following the Management of Ameloblastomas via Targeted Therapies – Pathological and Clinical Perspectives

Hirschhorn,

Grynberg,

Campino

et al. 2024

Head and Neck Pathol

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Purpose Current standard of care for ameloblastoma (conventional/unicystic - mural type) usually mandates extensive bone resection that frequently necessitates immediate reconstruction with serious sequelae, especially among young patients. BRAF-mutated ameloblastomas can be targeted by BRAF inhibitors to markedly reduce their size, enabling conservative removal of residual tumor. We aimed to characterize the effect of post-treatment histomorphologic changes. Methods Study included 14 patients, 11 mandibular and three maxillary tumors. Cases with very minimal residual tumor were defined as near-complete response, while those with mostly vital residual tumor as partial response. The epithelium component was scored for architectural and cellular changes, stroma - for fibrosis, inflammation and new bone formation, on a 3-tired score system: 0–no, 1–focal and 3–frequent changes. The mean scores of each parameter, total epithelium and total stroma were calculated and related to duration of treatment. Differences in the mean scores were investigated for mandibular tumors with near-complete response (n = 3) and partial response (n = 8). Results There were no significant differences in mean epithelium or stroma scores between tumors with near-complete and those with partial response (2.22 ± 0.68 versus 2.08 ± 0.43, p = 0.55; 1.41 ± 1.04 versus 1.43 ± 0.44, p = 0.27), suggesting that ameloblastomas have potential to undergo complete response to targeted treatment. This is probably dependent upon tumor/patient/treatment-related factors. Response to treatment appears to be predictable with neoplastic epithelium being first, while the stromal response increases during treatment, the entire process expanding over weeks-to-months. Conclusion Albeit preliminary, these are the first comprehensive histomorphologic findings on BRAF-treated ameloblastomas. Analyzing the suggested parameters in tumors with partial response, should highlight which tumor component has responded/failed to respond. This could serve as a basis for decision-taking toward subsequent steps in adjuvant treatment (e.g., follow-up, conservative surgery, modifications/changes in treatment regimen, combinations of approaches), with a prime aim of jaw preservation and minimal risk of sequelae.

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Treatment of a BRAF V600E Positive Ameloblastoma in a Pediatric Patient with MEK Inhibitor Monotherapy

Cited by 7 publications

References 31 publications

Genomic profiling and precision medicine in complex ameloblastoma

Genomic profiling and precision medicine in complex ameloblastoma

Gene Mutations in the FGF-MAPK Signaling Pathway and Targeted Therapy in Ameloblastoma

Histopathologic and Molecular Insights Following the Management of Ameloblastomas via Targeted Therapies – Pathological and Clinical Perspectives

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