Correlating Chemical Sensitivity with Low Level Activation of Mechanotransduction Pathways in Hematologic Malignancies

Large-scale screening has revealed that human hematopoietic cancer cell lines are generally more sensitive to various classes of drugs than cell lines established from solid tumors. A detailed examination of data in the Cancer Therapeutics Response Portal ( http://portals.broadinstitute.org/ctrp/ ) suggests that this enhanced sensitivity is due to lower basal levels of activation of TAZ-TEAD mechanotransduction pathways in hematopoietic versus non-hematopoietic cells. Translation inhibitors such as omacetaxine mepesuccinate (homoharringtonine) fall into this category of hematopoietic-selective compounds. Moreover, additional molecular determinants of sensitivity suggest that homoharringtonine might show therapeutic efficacy in certain patients with advanced hematologic malignancies despite activation of these pathways.