PIK3CA mutations are associated with resistance to HER2-targeted agents. PI3K inhibitors are potentially effective in overcoming trastuzumab resistance caused by PIK3CA mutations. S6K phosphorylation is a possibly useful pharmacodynamic marker in HER2-targeted therapy.

The MBP-QP method is simple, sensitive, and-intriguingly-reflective of clinical course, compared with the other three mutation-detection systems. Thus, the MBP-QP method is an ideal noninvasive monitoring system for detecting T790M in plasma samples.

: Our novel detection systems for EGFR mutations could be useful not only at the beginning of treatment but also for monitoring using plasma DNA for deciding appropriate treatment, including rechallenge with EGFR-tyrosine kinase inhibitors.

In a search for a human sequence related to a recently identified type I cytokine receptor δ1, which turned out to be a receptor subunit for a cytokine called TSLP, we have now identified a novel human type I cytokine receptor from a human T lymphocyte cDNA library. The deduced amino acid sequence of 371 residues has a typical signal sequence and a membrane-spanning region. The mature protein is predicted to have a molecular mass of 39,698 Da. The N-terminal extracellular region contains two fibronectin type III-like domains, four conserved cysteine residues, and a WSXWS box-like motif. The C-terminal intracellular region contains box 1 and box 2-like motifs. Thus, it has common characteristics of type I cytokine receptor family members, and we tentatively termed this protein CRLF2, which stands for cytokine receptor-like factor 2. Northern blot analysis revealed CRLF2 mRNA in liver, kidney, heart, and skeletal muscle. The fetal liver also expresses CRLF2 transcripts. The gene for CRLF2 was mapped to the pseudoautosomal region, Xp22.3 and Yp11.3 by FISH analysis, a region where genes encoding the IL-3 receptor α and the GM-CSF receptor α chains are also located. The biological function of this newly identified receptor is now under investigation.

We present a novel cancer marker-free CTC enrichment method by size-based filtration and immunomagnetic negative selection followed by dielectrophoretic concentration for direct detection of genetic mutations in rare cancer cells suspended in whole blood.