New generation approaches revive BET protein inhibitors in solid tumors

BET proteins, especially BRD4, drive oncogenic transcription in solid tumours. First‑generation inhibitors (JQ1, molibresib, birabresib) showed preclinical promise but failed clinically due to modest efficacy, dose‑limiting thrombocytopenia, and resistance (isoform switching, compensatory PI3K/AKT/WNT signalling).