The American Association for Cancer Research launched a new journal, Cancer Discovery, at its annual meeting this week. In the new journal's first edition, researchers from around the US present their characterization of KRAS rearrangements in metastatic prostate cancer. The team used an integrative genomics approach called amplification breakpoint ranking and assembly analysis, and found a gene fusion of KRAS with the enzyme UBE2L3, the knockdown of which "attenuates cell invasion and xenograft growth." Further, in NIH3T3 cells, UBE2L3 attenuates MEK/ERK signaling and instead signals via AKT and p38 MAPK pathways, suggesting that "this aberration may drive metastatic progression in a rare subset of prostate cancers," the authors write.
Also in Cancer Discovery this week, researchers in the US, Ireland, and Sweden say leukocyte complexity predicts survival in breast cancer patients and functionally regulates response to chemotherapy. Macrophage abundance and T-cell abundance in breast cancer represent prognostic indicators for recurrence-free and overall survival in breast cancer, the authors write. The team also found that cytotoxic therapies induce mammary epithelial cells to produce monocyte/macrophage recruitment factors, including CSF1 and interleukin-34. "Blockade of macrophage recruitment with CSF1R-signaling antagonists, in combination with paclitaxel, improved survival of mammary tumor-bearing mice by slowing primary tumor development and reducing pulmonary metastasis," the researchers say. "These improved aspects of mammary carcinogenesis were accompanied by decreased vessel density and appearance of antitumor immune programs fostering tumor suppression in a CD8+ T-cell–dependent manner."
And finally in Cancer Discovery this week, researchers at Johns Hopkins and Harvard present findings from a novel, two-stage transdisciplinary study, which identified the drug Digoxin — which is used to treat congestive heart failure — as a possible treatment for prostate cancer. The researchers conducted an in vitro prostate cancer cell cytotoxicity screen of more than 3,000 known compounds, and Digoxin emerged as a leading candidate to treat prostate cancer, given its ability to inhibit proliferation of cancer cells. In a screen of prostate cancer risk in more than 47,000 men, the team found that those already taking Digoxin had a lower risk of prostate cancer than those men not taking Digoxin. "Digoxin was highly potent in inhibiting prostate cancer cell growth in vitro, and its use was associated with a 25 percent lower prostate cancer risk," the team writes. "Our two-stage transdisciplinary approach for drug repositioning provides compelling justification for further mechanistic and possibly clinical testing of the leading nonchemotherapy candidate, digoxin … as a drug for prostate cancer treatment."