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Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed.Activator protein 1 (AP-1) has a key role in several cellular processes.Targeting AP-1 signaling pathways is therapeutic for cancer and inflammation.Natural bioactive compounds are of much interest in cancer prevention and therapy.Natural bioactive compounds modulate AP-1-associated signaling pathways in cancer.