The intratumor heterogeneity of cell signaling fa

Authors: S Ramon y Cajal L De MattosArruda N Sonenberg J Cortes V Peg

Publish Date: 2014/07/25

Volume: 16, Issue: 11, Pages: 937-941

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Abstract

Breast cancers and most malignant tumors are composed of heterogeneous tumor cells both at genetic and morphological levels intratumor heterogeneity can be one underlying cause of therapeutic resistance Classical studies have focused on analyses of the relationship between primary tumors and metastatic dissemination and on subclone evolution However it should be noted that tumor heterogeneity at the level of protein expression proteomics has not been yet studied in depth The differences in protein expression also can play an important role in elucidating the relationship between intratumor heterogeneity and resistance to systemic therapy In fact in human tumors there is not always a homogeneous expression of many of the crucial factors involved in cell signaling such as pMAPK pAKt pMTOR even with constitutive oncogenic alterations upstream such as HER2 PI3 K Conversely two of these factors peIF4E and p4EBP1 which are downstream and control protein translation show a diffuse and strong protein expression In summary most of cell signaling factors show a heterogeneous expression regardless of oncogenic alterations Tissue heterogeneity could be driven by local factors including hypoxia The fact that the phosphorylation of crucial proteins such as 4EBP1 and eIF4E is observed homogeneously throughout most tumors and are druggable opens the chance to get real potential targets in cancer therapy

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