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Erb-B2 receptor tyrosine kinase 3 (ERBB3) mRNA is the transcript that encodes the HER3 protein, a member of the human epidermal growth factor receptor (EGFR) family [1]. While the resulting ERBB3 protein lacks significant intrinsic kinase activity, it serves as a critical scaffold for the recruitment of phosphoinositide 3-kinase (PI3K) and activates the AKT survival pathway through heterodimerization with other ERBB family members like HER2 or EGFR [2]. Targeting the ERBB3 mRNA directly, rather than the protein, offers a strategy to completely ablate the production of all HER3 isoforms, including those that might lack the extracellular domains targeted by monoclonal antibodies [3]. This approach typically utilizes antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) to induce the degradation of the mRNA transcript via RNase H or the RNA-induced silencing complex (RISC) [4]. Clinically, ERBB3 mRNA levels are often elevated in various solid tumors, including breast, lung, and colorectal cancers, where they contribute to oncogenesis and resistance to standard-of-care therapies [5]. Therapeutic candidates like EZN-3920 have been investigated to silence ERBB3 expression at the pre-translational level to overcome these resistance mechanisms [3].
Antisense oligonucleotide-mediated degradation of mRNA via RNase H recruitment or RNA interference (RNAi) to prevent protein synthesis.
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