Epidermal
growth factor receptor (EGFR) is an oncogenic drug target
and plays a critical role in several cellular functions including
cancer cell growth, survival, proliferation, differentiation, and
motility. Several small-molecule tyrosine kinase inhibitors (TKIs)
and monoclonal antibodies (mAbs) have been approved for targeting
intracellular and extracellular domains of EGFR, respectively. However,
cancer heterogeneity, mutations in the catalytic domain of EGFR, and
persistent drug resistance limited their use. Different novel modalities
are gaining a position in the limelight of anti-EGFR therapeutics
to overcome such limitations. The current perspective reflects upon
newer modalities, importantly the molecular degraders such as PROTACs,
LYTACs, AUTECs, and ATTECs, etc., beginning with a snapshot of traditional
and existing anti-EGFR therapies including small molecule inhibitors,
mAbs, and antibody drug conjugates (ADCs). Further, a special emphasis
has been made on the design, synthesis, successful applications, state-of-the-art,
and emerging future opportunities of each discussed modality.
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