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The 'hallmarks of cancer' are generally accepted as a set of genetic and epigenetic alterations that a normal cell must accrue to transform into a fully malignant cancer. It follows that therapies designed to counter these alterations might be effective as anti-cancer strategies. Over the past 30 years, research on the BCL-2-regulated apoptotic pathway has led to the development of small-molecule compounds, known as 'BH3-mimetics', that bind to pro-survival BCL-2 proteins to directly activate apoptosis of malignant cells. This Timeline article focuses on the discovery and study of BCL-2, the wider BCL-2 protein family and, specifically, its roles in cancer development and therapy.

Original publication




Journal article

Publication Date





99 - 109


Animals, Apoptosis, Biphenyl Compounds, Cell Death, Gene Expression Regulation, Neoplastic, Genes, bcl-2, Humans, Mice, Molecular Targeted Therapy, Multigene Family, Neoplasms, Nitrophenols, Piperazines, Proto-Oncogene Proteins c-bcl-2, Sulfonamides, bcl-2-Associated X Protein