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AACR 2023: Researchers Identify Cell Signaling Pathways Activated by ETV6::NTRK3 Fusions

By: Amy MacDonald, MS
Posted: Thursday, May 4, 2023

The interactome is defined as the entirety of interactions between biologic macromolecules of a cell. Because chromosomal translocations such as t(12; 15)(p13; q25)—which lead to expression of oncogenic fusion proteins, including ETV6::NTRK3—are increasingly associated with oncogenic transformation, an understanding of the cellular signaling pathways activated by such oncofusions is warranted. Markku Varjosalo, PhD, of the University of Helsinki, and colleagues used proximity labeling mass spectrometry to investigate the interactome of ETV6::NTRK3 oncofusions. Their results were presented at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract LB006/6).

“We identify 237 high-confidence interactors, which link EN fusions to several key signaling pathways, including ERBB, insulin, and JAK/STAT,” the investigators stated.

The researchers assessed the effects of specific ETV6::NTRK3 oncofusion variants on these cell signaling pathways. They found that the pan-NTRK inhibitor selitrectinib (LOXO-195) inhibited the oncogenic activity of EN2, the most common variant. The systems-level analysis employed by the researchers defined the molecular framework in which ETV6::NTRK3 oncofusions operate to promote cancer.

Disclosure: The study authors reported no conflicts of interest.

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