In Cancer Research this week, US and Canadian researchers define a new subgroup of Sonic hedgehog-driven medulloblastomas. In this subgroup, the team found, the Sonic hedgehog and CXCR4 pathways are co-activated. They were found to be most common in the youngest patients and were associated with desmoplastic histology. "In contrast to tumors activating SHH but not CXCR4, co-activated tumors exhibited greater expression of Math1 and cyclin D1," the authors write. "Treatment with the CXCR4 antagonist AMD3100 inhibited cyclin D1 expression and maximal tumor growth in vivo."
Also in Cancer Research this week, a team led by researchers at Weill Cornell Medical College report a novel method of analysis of how drugs can be repositioned for cancer treatment. The team describes a "[drug off target effects]-based method to repurpose drugs for cancer therapeutics, based on transcriptional responses made in cells before and after drug treatment." Specifically, the researchers say their method accurately predicts clinical responses to more than 90 percent of drugs approved by the FDA, and more than 75 percent of experimental clinical drugs. "Mechanistic investigation of OTEs for several high-ranking drug-dose pairs suggested repositioning opportunities for cancer therapy, based on the ability to enforce retinoblastoma-dependent repression of important E2F-dependent cell-cycle genes," the authors write. "Together, our findings establish new methods to identify opportunities for drug repositioning or to elucidate the mechanisms of action of repositioned drugs."
Finally in Cancer Research this week, researchers in the US and China report that the HMGB1 gene can promote drug resistance in osteosarcoma. In human osteosarcoma cells, the team found that the chemotherapy drugs doxorubicin, cisplatin, and methotrexate each induced an up-regulation of HMGB1, and that a subsequent knock-down of the gene restored the cells' sensitivity to chemotherapy both in vivo and in vitro. "Mechanistic investigation revealed that HMGB1 increased drug resistance by inducing autophagy, an intracellular self-defense mechanism known to confer drug resistance," the authors write. "Through its role as a regulator of autophagy, HMGB1 is a critical factor in the development of chemoresistance, and it offers a novel target for improving osteosarcoma therapy."