Interferon/STAT1 and neuregulin signaling pathways are exploratory biomarkers of cetuximab (Erbitux®) efficacy in KRAS wild-type squamous carcinomas: a pathway-based analysis of whole human-genome microarray data from cetuximab-adapted tumor cell-line models.

KRAS mutation status is being used as the sole biomarker to predict therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A significant number of mCRC patients with KRAS wild-type (WT) tumors, however, do not benefit from cetuximab. We are also lacking efficacy predictors in head and neck squamous cell carcinomas with an intact KRAS signaling and in non-small cell lung cancer in which KRAS mutations do not predict cetuximab efficacy.

Pathway-focused proteomic signatures in HER2-overexpressing breast cancer with a basal-like phenotype: new insights into de novo resistance to trastuzumab (Herceptin).

Pioneering clinical studies in de novo refractoriness to the anti-HER2 monoclonal antibody trastuzumab have suggested that HER2 gene-amplification can take place also in a basal-like molecular background to generate basal/HER2+ tumors intrinsically resistant to trastuzumab. Here, we first investigated the unique histogenesis of the basal/HER2+ phenotype in breast carcinomas. The presence of basal CK5/CK6 cytokeratin expression in HER2+ tumors revealed a significant overlap in the histological features of HER2+/CK5/6+ and basal-like breast carcinomas.

Serine 2481-autophosphorylation of mammalian target of rapamycin (mTOR) couples with chromosome condensation and segregation during mitosis: confocal microscopy characterization and immunohistochemical validation of PP-mTOR(Ser2481) as a novel high-contrast mitosis marker in breast cancer core biopsies.

The prognostic abilities of breast cancer gene expression signatures are due mostly to the detection of proliferation activity. One of the strongest, yet simple and well-reproducible proliferation-associated prognostic factors is the mitotic activity index (MAI). However: a) counting mitotic figures is regarded by many histopathologists as cumbersome and time-consuming, and b) most available immunohistochemical markers are much weaker predictors than the MAI.

Mitotic kinase dynamics of the active form of AMPK (phospho-AMPKalphaThr172) in human cancer cells.

When interrogating the activation status of AMP-activated protein kinase-measured as AMPKalpha(Thr172) phosphorylation-in tissue sections of human carcinomas and in cultured human cancer cells, the spatiotemporal dynamics of AMPK activity during the G(1)/S-to-M-phase transition strikingly resembles that of well-characterized "chromosomal passenger" proteins such as Aurora B, INCENP or Histone H3. The mitotic kinase behavior of the active form of AMPK may represent a candidate molecular link through which energy status directly influences tumorigenesis. A definitive elucidation of phospho-AMPKalpha(Thr172) in coordinating the chromosomal and cytoskeletal events of mitosis might radically amend our current perception of other AMPK-related diseases such as obesity, cardiac hypertrophy or accelerated aging syndromes.