In Cancer Research this week, researchers from the Ovarian Cancer Association Consortium report on the associations between ovarian cancer risk and inflammation-related gene variants. The team genotyped SNPs in a large panel of inflammatory genes in 903 ovarian cancer cases and 1,037 controls. They found an association between cancer risk and "SNPs rs17561 and rs4848300 in the interleukin gene IL1A," which varied by histological subtype. "IL1A rs17561, which correlates with numerous inflammatory phenotypes, was associated with decreased risk of clear cell, mucinous, and endometrioid subtype, but not with the most common serous subtype," the authors write. "Genotype at rs1864414 in the arachidonate 5-lipoxygenase ALOX5 was also associated with decreased risk."
Also in Cancer Research this week, researchers in Germany explore the "mutanome of B16F10 melanoma," and its potential for tumor vaccination. "The multiplicity of gene mutations derived from clonal heterogeneity represents an ideal setting for multiepitope tumor vaccination," the authors write. They identified 962 non-synonymous somatic point mutations in a melanoma cells line, 563 of which mutations were in expressed genes. "Potential driver mutations occurred in classical tumor suppressor genes and genes involved in proto-oncogenic signaling pathways that control cell proliferation, adhesion, migration, and apoptosis," the team says. "The immunogenicity and specificity of 50 validated mutations was determined by immunizing mice with long peptides encoding the mutated epitopes. One-third of these peptides were found to be immunogenic, with 60 percent in this group eliciting immune responses directed preferentially against the mutated sequence as compared with the wild-type sequence." These findings show a comprehensive picture of the melanoma cell line mutanome, they add, and may help in developing personalized immunotherapeutics for cancer patients.
And finally in Cancer Research this week, an international team of researchers reports that inhibition of cathepsin B in breast cancer patients may limit the risk of bone metastasis. The team inhibited cathepsin B in a bone metastasis model of breast cancer, and found that it reduced collagen degradation in vitro and bone metastasis in vivo. "Similarly, intraperitoneal administration of the highly selective cathepsin B inhibitor CA-074 reduced metastasis in tumor-bearing animals, a reduction that was not reproduced by the broad spectrum cysteine cathepsin inhibitor JPM-OEt," the team writes. "Notably, metastasis suppression by CA-074 was maintained in a late treatment setting, pointing to a role in metastatic outgrowth."