In the British Journal of Cancer this week, a group of European researchers presents findings from phase I and open-label phase II studies of sorafenib and dacarbazine as a treatment for advanced melanoma. In the phase I study, the team analyzed maximum doses for acceptable toxicity. Then in the phase II study, 83 participants received the combination therapy, and the overall response rate was 12 percent, and stable disease was seen in 37 percent, the authors write. "Oral sorafenib combined with dacarbazine had acceptable toxicity and some antineoplastic activity against metastatic melanoma," they add.
Also in the British Journal of Cancer this week, researchers in the US and UK present the identification and evaluation of a potent novel ATR inhibitor in breast and ovarian cancer cell lines. ATR has a key role in the signaling of stalled replication forks and the repair of damaged DNA. In analyzing the activity of compound NU6027 in breast and ovarian cancer cell lines, the team found it to be a potent inhibitor of cellular ATR activity. "NU6027 inhibits ATR, impairing G2/M arrest and homologous recombination thus increasing sensitivity to DNA-damaging agents and PARP inhibitors," the authors write. "It provides proof of concept data for clinical development of ATR inhibitors."
Finally in the British Journal of Cancer, researchers in Japan differentiate the roles of STAT3 depending on the mechanism of STAT3 activation in gastric cancer cells. "The MET-tyrosine kinase inhibitor and cell transfection with a small interfering RNA specific for MET mRNA inhibited STAT3 phosphorylation in MET-activated cells, indicating that STAT3 activation is linked to MET signaling," the authors write. The researchers also found evidence to suggest that inhibition of STAT3 contributes to MET-TKI-induced apoptosis. "Our data thus show that activated STAT3 contributes to either cell survival or motility in gastric cancer cells, and that these actions are related to different mechanisms of STAT3 activation," the team adds.