Decoding and unlocking the BCL‐2 dependency of cancer cells

Abstract : Cancer cells are subject to many apoptotic stimuli that would kill them were it not for compensatory prosurvival alterations. BCL‐2‐like (BCL‐2L) proteins contribute to such aberrant behaviour by engaging a network of interactions that is potent at promoting survival but that is also fragile: inhibition of a restricted number of interactions may suffice to trigger cancer cell death. Currently available and novel compounds that inhibit these interactions could be efficient therapeutic agents if this phenotype of BCL‐2L dependence was better understood at a molecular, cellular and systems level and if it could be diagnosed by relevant biomarkers.