Beyond molecular tumor heterogeneity: protein synthesis takes control

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

Han et al. [107] p-eIF4E and p-MNK1 are independent prognostic factors in nasopharyngeal carcinoma Zheng et al. [63] Kidney p-4E-BP1 is associated with poor prognosis in Xp11.2 translocated renal cell carcinoma Qu et al. [108] p-4E-BP1 and eIF4E are independent prognostic factors in clear cell renal cell carcinoma Campbell et al. [109] p-4E-BP1 is a prognostic predictor in patients with metastatic renal cell carcinoma Nishikawa et al. [110] Liver eIF4E overexpression is an independent indicator for overall survival in hepatocarcinoma Jiang et al. [64] p-4E-BP1 is overexpressed in cholangiocarcinomas with poor differentiation and lymph node metastasis, and is an independent prognostic factor Fang et al. [111] Lung p-4E-BP1 expression is associated with poor prognosis in small-cell lung cancer Roh et al. [66] p-4E-BP1 Thr70 predicts poor prognosis in non-small-cell lung cancer Lee et al. [112] p-4E-BP1 and eIF4E are prognostic factors in stage I lung adenocarcinoma Seki et al. [113] High eIF4E expression correlates with poor prognosis in lung adenocarcinomas Wang et al. [114] Melanoma eIF4E is associated with melanoma thickness and overall survival Khosravi et al. [68] p-4E-BP1 is associated with poor survival in melanoma O'Reilly et al. [115] Ovary p-4E-BP1 is a prognostic factor in ovarian cancer Castellvi et al. [56] Stomach p-eIF4E is overexpressed in tumors with lymph node metastasis Tapia et al. [116] p-4E-BP1 is a prognostic factor in gastric cancer patients and correlates with advanced stage Jiao et al. [117] have been obtained from preclinical models of diffuse large B cell lymphoma, non-small-cell lung carcinoma, and breast adenocarcinoma. Moreover, the inhibitor eFT508 enhances the efficiency of anti-PDL1 checkpoint blockade inhibitors [95] . Similarly, blockage of 4E-BP1 phosphorylation by inhibition of upstream signaling activity (e.g., mTOR) will decrease eIF4F levels and dampen cap-dependent translation and tumor cell growth [40] .