Sentence examples for vertical blockade from inspiring English sources
The emphasis is now shifting to targeting networks and pathways with combinations of signalling drugs, either in parallel (so-called combined horizontal blockade) or in series (combined vertical blockade).
On the other hand, the rationale for combination therapy is inhibition of either a single pathway (vertical blockade) or different pathways (horizontal blockade) in order to increase efficacy and reduce toxicity [ 7].
The future development of these promising inhibitors should therefore focus on combination regimens, including the concomitant or sequential blockade of signaling pathways, e.g., horizontal blockade of the PI3K-AKT-mTOR and RAS-RAF-MEK pathways or vertical blockade of the PI3K/AKT/mTOR and IGF pathways.
In the article by Wilky and colleagues, the investigators present findings from a phase I study assessing the vertical blockade of MEK1/2 and insulin growth factor-1 receptor (IGF-1R) with the small molecule selumetinib (AstraZeneca, Macclesfield, UK) and monoclonal antibody cixutumumab (ImClone Systems Inc., Bridgewater, NJ, USA), respectively (Wilky et al, 2014).
Recent pre-clinical examples of horizontal blockade in breast cancer include mitogen-activated protein kinase kinase (MEK) inhibition combined with PI3K in basal-like breast cancers [ 19], while vertical blockade includes enhancing responsiveness to HER2-directed therapies (trastuzumab, pertuzumab or lapatinib) by combination with a potent PI3K inhibitor [ 20].
Ultimately, a greater understanding of the biology and compensatory mechanisms will allow the partnering of key signal transduction inhibitors together to provide maximal "vertical" or "horizontal" blockade with further preclinical and clinical studies planned to examine possible synergistic combinations with endocrine therapy.
In our study, we evaluated vertical inhibition of the IGF-1R pathway based on in vitro evidence that simultaneous blockade of upstream and downstream targets increased cell death.
Vertical fiscal imbalance.
