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

Abstract

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.

DUOX2 promotes the progression of colorectal cancer cells by regulating the AKT pathway and interacting with RPL3

“…For instance, RP can affect the growth, senescence, apoptosis, invasion, radiation and drug therapy resistance of cancer cells through various mechanisms. Previous studies have revealed that both hematopoietic and non-hematopoietic cancer cell lines with increased RPL3 expression exhibit enhanced sensitivity to drugs ( 30 ), while the loss of RPL3 makes chemotherapy drugs ineffective ( 31 ). RPL3 can upregulate p21 expression at the transcriptional level ( 31 ), and participate in the cell response to chemotherapy, acting as a critical regulator of the cell cycle, apoptosis and DNA repair ( 31 ).…”