Newly Discovered Fusion Proteins for Targeting Cancer

Release Date: 02-Nov-2020

The groundbreaking approval of the drug Gleevec (imatinib) in the year 2001 and further the identification chromosomal rearrangements that later on leads to oncogenic gene fusions has completely led to the transformation of the targeted therapies in the oncology sector. The drug that got approved in the year 2001 is considered to be a magic bullet, which indeed targets BCR-ABL1 gene fusion protein in the patients suffering from chronic myeloid leukemia.

The approval of the drug Gleevec for the cancer patients is estimated to be the result of advanced sequencing technologies that are available in the market. With the help of several advanced sequencing technologies, researchers have remained successful in identifying large number of cancer-driving gene fusions as well as prompting the development of number of new therapeutic drugs that are directed towards the alterations. The agents developed by the US FDA acts against the mechanism of action of BCR-ABL protein as well as ALK, RET, NTRK, and FGFR2 fusions. The researchers that are inclined towards finding fusion proteins are also seeking interest towards involving the NRG1 gene to the long list of the targets. As per the researchers, the gene NRG1 is found in very low rates in case of different types of cancers. It has also been found that all the above-mentioned fusions are extremely oncogenic and can be targeted by drugs as a treatment.

An old study also focuses towards identifying a novel type of genomic aberration in lung adenocarcinomas. In that respective study, first 6 exons of the CD74 gene were fused to the exons of the NRG1 gene that encode its EGF-like receptor-binding domain. The researchers inclined towards the respective study demonstrated the gene fusion drives the overall development of cancer as on the surface of the cells, NRG1 EGF-like domain is overexpressed, otherwise this type of cancer is devoid of NRG1 expression. It is analysed by the researchers that NRG1 EGF-like domain do function as a ligand for HER3 as well as also triggers heterodimerization of triggers HER2-HER3 and subsequent intracellular signaling using the PI3K/AKT pathway.