Beyond molecular tumor heterogeneity: protein synthesis takes control

Ramon y Cajal, Santiago; Castellvi, Josep; Hümmer, Stefan; Peg, Vicente; Pelletier, Jerry; Sonenberg, Nahum

The consequences of this pervasive lack of uniformity between cancer cells are grim for patients. It is a major cause of treatment failure in many patients, particularly in those treated with molecular targeted therapies [21] . If a fraction of cancer cells in the tumor do not express a particular drug target or have evolved to no longer be dependent on its presence/activity, then it stands to reason that these cells will fail to be eliminated by targeted therapies. A case in point is HER2+ (human epidermal growth factor receptor 2) breast cancers, with the classification requiring that only 30% of the cells have to stain positive for HER2 by immunocytochemistry. Clearly, treatment with anti-HER2 therapies cannot be expected to be curative in such a context. Similarly, therapies based on rapamycin fail because of the uneven and heterogeneous expression of p-mTOR [22] [23] [24] .