In Cancer Cell this week, researchers in Boston and Chicago discuss a way to exploit weaknesses in cancer cells in the development of a combination therapy for Ras-driven tumors. The team shows that enhancing proteotoxic stress induces tumor regression in aggressive mouse models of two Ras-driven cancers — Nf1-deficient malignancies and Kras/p53 mutant lung cancer — but only when combined with rapamycin. The agents work together to promote stress in the cancer cells, which results in catastrophic mitochondrial damage, the authors write. "Notably, the mechanism by which these agents cooperate reveals a therapeutic paradigm that can be expanded to develop additional combinations," they add.
Also in Cancer Cell this week, a team led by investigators at the St. Jude Children's Research Hospital reports its use of an integrated, high-throughput in vitro and in vivo screen to identify treatments for ependymoma, a chemoresistant brain tumor. In a mouse model, the team combined multicell high-throughput screening, kinome-wide binding assays, and in vivo efficacy studies to identify kinases within the insulin signaling pathway and the centrosome cycle that serve as regulators of ependymoma cell proliferation. The kinases' corresponding inhibitors could serve as potential therapies, the authors write.
And finally in Cancer Cell this week, a team of researchers in the US shows that the Rho kinase regulates the survival and transformation of cells that carry oncogenic forms of the KIT, FLT3, and BCR-ABL genes. The team found that inhibition of Rho kinase in oncogene-bearing cells impaired their growth, and prolonged the life span of test mice. In addition, the authors write, "Downstream from Rho kinase, rapid dephosphorylation or loss of expression of myosin light chain resulted in enhanced apoptosis, reduced growth, and loss of actin polymerization in oncogene-bearing cells leading to significantly prolonged life span of leukemic mice."