NTRK Somatic Fusions and Tumor Agnostic Treatment in Pediatric Cancers

Abstract

Neurotrophic tyrosine receptor kinase (NTRK) gene rearrangements have been recently identified and developed as one of the biomarkers that have been utilized as new targets for cancer therapy. NTRK gene fusions have taken their place in individualized targeted therapy by being used as a predictive (diagnostic) biomarker as well as a treatment target. Selective inhibitors of NTRK fusion proteins have potent efficacy in the treatment of NTRK fusion-positive solid tumors. Detection of these fussions have become important since the finding of new drugs for which U.S. Food and Drug Administration (FDA) granted approval are used on the treatment of patients who has NTRK fussions positive cansers. Clinical trials have shown that first generation tyrosine receptor kinase (TRK) inhibitors, larotrectinib (Vitrakvi, Bayer HealthCare Pharmaceutical Inc, New Jersey, U.S.) and entrectinib (Rozlytrek, Genentech Inc, California, U.S.), have potent efficacy in the treatment of NTRK fusion positive cancers. In the future, with the increase in the number of comprehensive studies on these drugs further information will become available and beneficial.

Keywords

• NTRK fussion
• tumor agnostic treatment
• precision medicine
• larotrectinib
• entrectinib

Çocukluk Çağı Kanserlerinde NTRK Somatik Füzyonları ve Tümör Agnostik Tedavi

Abstract

Nörotrofik tirozin reseptör kinaz (NTRK) geni yeniden düzenlemeleri yakın zamanda kanser tedavisi için yeni hedefler olarak ortaya konulan biyobelirteçlerden (biyomarker) bir tanesi olarak tanımlanmış ve geliştirilmiştir. NTRK gen füzyonları öngörücü (prediktif-tanısal) bir biyobelirteç olarak kullanılmasının yanı sıra tedavi hedefi olarak da kullanılarak bireyselleştirilmiş hedef tedavide yerini almıştır. NTRK füzyon proteinlerinin selektif inhibitörleri, NTRK füzyon pozitif solid tümörlerin tedavisinde güçlü etkinliğe sahiptir (tümör-agnostik tedavi). Tümörlerinde NTRK füzyonları saptanan hastaların tedavisinde etkili olan FDA (Amerika Birleşik Devletleri Gıda ve İlaç Yönetimi) onaylı yeni tedavilerle birlikte, bu füzyonların test edilmesi önemli hale gelmiştir. Yapılan klinik çalışmalar birinci nesil tirozin reseptör kinaz (TRK) inhibitörleri olan larotrectinib ve entrectinibin NTRK füzyonu pozitif kanserlerin tedavisinde yüksek oranda başarılı olduğu görülmüştür. İlerleyen zamanlarda bu ilaçlar üzerine geniş kapsamlı araştırmaların sayısının artması bu ilaçlar hakkında daha fazla bilgiyi mevcut kılacak ve faydalı olacaktır.

Keywords

• NTRK füzyonu
• tümör agnostik tedavi
• hassas tıp
• larotrectinib
• entrectinib

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