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Upfront BRAF Inhibitor Treatment for Ameloblastoma

Overview

Ameloblastoma is a disorder of the jaw involving abnormal tissue growth. It is a slow-growing tumor that develops in the space behind our molar or back teeth. The condition is considered to be the most common odontogenic epithelial tumor, and often results in an enlarged jaw and facial deformities.
The standard therapy for ameloblastoma is radical bone resection, which usually involves subsequent functional, aesthetic & psychological impairments. The procedure often involves the removal of healthy tissues around the tumor to lower the chances of recurrence, as a high recurrence rate is a serious issue. Specifically, large ameloblastomas are known to be associated with increased rates of recurrence.
Accordingly, many require reconstructive surgery to replace the bone and tissues removed and prevent visible disfigurement.
Following recent successful clinical trials and FDA approval, anti-BRAF inhibitor therapy, which spares the trauma of aesthetic deformities as well as functional and psychological impairments, could prove to have a profound impact on patients’ quality of life.

Inhibitor Treatment

The Role of Anti-BRAF Mutation

The B-RAF proto-oncogene, serine/threonine kinase (BRAF) gene is involved in regulating biological processes, such as cell proliferation, differentiation, and apoptosis. Anti-BRAF mutations have been found to play a critical role in most cases of ameloblastoma.
BRAF gene mutations have been identified in ameloblastomas, with one mutation (BRAF V600E) occurring frequently. The high incidence of BRAF V600E enables the use of selective inhibitors in a neoadjuvant setting to treat advanced-stage ameloblastoma.
Recent studies indicate that the use of upfront BRAF inhibitor treatment results in substantial tumor regression, allowing for non‐mutilating complete surgical removal, bone regeneration, and organ preservation.

How Does Upfront BRAF Inhibitor Treatment Work?

The upfront therapy is given to patients with confirmed BRAF V600E ameloblastoma (60%-70% of ameloblastoma patients) by means of an orally administered targeted drug called Dabrafenib (also known as Tafinlar). Depending on each patient’s specific condition, Trametinib (also known as Mekinist) may also be administered. Both medications are approved by the FDA for treating various conditions, including ameloblastoma.
The adjuvant therapy is meant not only to reduce the size of tumors, but also to aid jawbone regeneration, thus allowing near-complete regeneration of the jawbone.
To help your body grow new, healthy cells, the therapy takes place over the course of a few months, subject to your individual response. While the minimum treatment duration is three months, the average is ten.
At Sheba, cancer treatment plans are tailored for each patient’s specific condition, taking into account how cancer affects your overall health and well-being.

Who is a candidate for upfront BRAF inhibitor therapy?

Most ameloblastomas with BRAF V-600E mutation occur in young adults (between the ages of 20 and 40), with gender not being a significant factor.
BRAF inhibitor therapy has been found to be effective at all stages of ameloblastoma in children and adults, and presents the first successful upfront rational therapy for ameloblastoma in young patients.

Potential side-effects

To date, a few side effects have been associated with upfront BRAF inhibitor treatment, namely:

  • Mild nausea during the first few days of treatment
  • Fever
  • Skin rash
  • Why chose Sheba for upfront BRAF inhibitor therapy?

    A comprehensive, advanced medical facility, recognized by Newsweek as one of the world’s top 10 hospitals, Sheba is steadfastly committed to providing patients with the most progressive treatments as its experts continually conduct groundbreaking research.
    The leading cancer treatment facility in Israel, Sheba’s Cancer Center takes a holistic approach to cancer care, providing patients with psychological, physiotherapy, and other services to support their overall wellbeing.

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