Small-cell lung cancer (SCLC) and some other cancers involve dysregulation of the transcription factor E2F, and apoptosis can be induced in those cells by blocking the interaction of the RxL sequence motif in E2F with cyclin A, which leads to hyperactivation of E2F. Researchers from Dana-Farber Cancer Institute and collaborators have developed macrocyclic peptides that inhibit this interaction and thereby hyperactivate E2F, leading to anticancer activity in various preclinical systems.