Akademik Veri Yönetim Sistemi
Kıvrak H., Sak S., Bozdayı A. M., Kuzu I. (Yürütücü)
Yükseköğretim Kurumları Destekli Proje, 2021 - 2022
ABSTRACT
The use of smart drugs in cancer treatment is becoming more common and important day by
day. In this process, which started with the introduction of Trastuzumab in breast cancer
patients showing HER2 gene amplification in the early 2000s and continued with the
introduction of small molecule inhibitors targeting specific genomic changes in lung cancers,
specific tumor subtypes of specific organs were targeted until 2018. In the future, if the tumor
shows a specific genomic change (as tumor agnostic), regardless of the location and name of
the tumor, it has been determined that patients benefit from drugs targeting this specific
genomic change, and the concept of tumor agnostic drug has entered the literature.
Pembrolizumab was the first tumor-agnostic drug approved for use. Then, since 2018, tumor
agnostic drugs targeting Neurotrophic receptor tyrosine kinase (NTRK) gene fusions have
been approved by the FDA and started to be used.
Gene fusions are the main or passenger mutation type that cause tumorigenesis in many
cancer types, especially in hematolymphoid malignancies and sarcoma group tumors.
Methods used to detect gene fusions; immunohistochemistry (IHC), fluorescent intisu
hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR) and new
generation sequencing (NGS) targeting DNA or RNA, which has been used more frequently
recently. ALK, whose oncogenic effects have been known for a long time, there are globally
accepted reference guidelines on which method to use and how to evaluate fusion-type
mutations. However, our knowledge about which method will be chosen in which patient
regarding newly discovered gene fusions that have become diagnostic/prognostic or
therapeutic targets is not so clear. NTRK gene fusions are also included in this group, and yet,
the literature discusses which method should be used to examine NTRK gene fusions with
tumor agnostic target drug in which tumors.
As an RT-PCR strategy, 5'3' imbalance studies offer an alternative to known gene fusion
detection methods. In contrast to the strategy used in classical RT-PCR, which requires
knowing the fusion partner, in the imbalance strategy, wild-type gene mRNA is targeted and
fusion interpretation is made by looking at the ratio of the 5' and 3' ends of the gene. A very
limited number of studies in the literature have shown that this method can also be used to
detect fusion-type mutations. There is no study using the imbalance strategy in the research of
the most sensitive, specific and cheapest method for detecting NTRK fusion, which is still
under discussion in the literature. This strategy, which will help to analyze all 3 members of
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the NTRK gene family, will take its place as a good alternative for fusion detection if its
usability is proven.
Keywords: NTRK fusion, ALK fusion, RT-PCR, 5’3’imbalance , Neoplasia