Role of eIF4A1 in triple-negative breast cancer stem-like cell-mediated drug resistance

In cap-dependent translation, the eukaryotic translation initiation factor 4A (eIF4A1) is an mRNA helicase is involved in unwinding of the secondary structure, such as the stem-loops, at the 5′-leader regions of the key oncogenic mRNAs. This facilitates ribosomal scanning and translation of the oncogenic mRNAs. eIF4A1 has a regulatory role in translating many oncoproteins that have vital roles in several steps of metastases. Sridharan et. al. have discovered and provide a novel insight into how eIF4A1 can play a regulatory role in drug resistance by influencing the levels of pluripotent Yamanaka transcription factors and ATP-binding cassette (ABC) transporters in triple-negative breast cancer (TNBC) stem-like cells. These findings may help us understand the molecular underpinnings of chemoresistance, especially in established metastases in TNBC. Importantly, eIF4A1 may form a novel clinical target in metastatic TNBC and the drug eFT226 from Effector Therapeutics targeting eIF4A1 is already in phase1-2 clinical trial.