publication date: Nov. 30, 2018
How we isolated the TRK oncogene
By Mariano Barbacid
AXA-CNIO Professor of Molecular Oncology,
Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid
I was very surprised to see in an issue of the NEJM earlier this year that Loxo Oncology had developed a selective TRK inhibitor, larotrectinib, and even more surprised to learn that TRK fusions occur in about 1 percent of all human cancers.
I always thought that the generation of the TRK oncogene that we isolated back in mid-1980s was a rather unusual event, so it would not have a significant relevance for cancer patients.
I guess, before massive sequencing, a one percent incidence could be considered an unusual event.
Those days were extremely exciting since we had just published three major discoveries in 1982 (Nature called it the “year of the oncogene” in an editorial):
The isolation of the first human cancer gene from a bladder tumor cell line,
Its identification as a member of the RAS gene family of oncogenes previously identified in mammalian sarcoma viruses (hence validating all the fantastic work done during the previous decade on retroviruses),
The identification of its mechanism of malignant transformation by a single point mutation, the first molecular alteration linked to human cancer.
All these discoveries were also made independently by Robert Weinberg, then an associated professor at MIT, and by Mike Wigler, then another young investigator starting his own … Continue reading How we isolated the TRK oncogene
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