Weekly Review of oncology literature compiled by Giuseppe Curigliano, Division of Medical Oncology

Pharmacogenomic Prediction of Anthracycline-Induced Cardiotoxicity in Children

Henk Visscher et al, JCO, Early release

2,977 single-nucleotide polymorphisms (SNPs) in 220 key drug biotransformation genes in a discovery cohort of 156 anthracycline-treated children from British Columbia with replication in a second cohort of 188 children from across Canada and further replication of the top SNP in a third cohort of 96 patients from Amsterdam.The team identified multiple genetic variants in SLC28A3 and other genes associated with anthracycline cardiotoxicity.Combined with clinical risk factors, genetic risk profiling might be used to identify high-risk patients who can then be provided with safer treatment options.

Phase II study of eribulin mesylate (E7389) in patients with metastatic castration-resistant prostate cancer stratified by prior taxane therapy

J. de Bono et al, Annals of Oncology, Early Release

108 men with histologically proven CRPC, with or without prior taxane exposure, were enrolled in an open-label, single-arm phase II trial. Patients received eribulin mesylate 1.4 mg/mq as a 2- to 5-min i.v. bolus infusion on days 1 and 8 of a 21-day cycle. PSA decreases of ≥50% were achieved in 22.4% and 8.5% of taxane-naive and taxane-pretreated patients, respectively. Grade 3 peripheral neuropathy occurred in none of the taxane-naive patients and 6.0% of taxane-pretreated patients. Eribulin mesylate demonstrated activity and a relatively favorable toxicity profile in metastatic CRPC.

Lung Cancer Signatures in Plasma Based on Proteome Profiling of Mouse Tumor Models

Ayumu Taguchi et al, Cancer Cell, 20, Issue 3, 289-299, 13 September 2011

The team investigated the potential of in-depth quantitative proteomics to reveal plasma protein signatures that reflect lung tumor biology. They compared plasma protein profiles of four mouse models of lung cancer with profiles of models of pancreatic, ovarian, colon, prostate, and breast cancer and two models of inflammation. A protein signature for Titf1/Nkx2-1, a known lineage-survival oncogene in lung cancer, was found in plasmas of mouse models of lung adenocarcinoma. An EGFR signature was found in plasma of an EGFR mutant model, and a distinct plasma signature related to neuroendocrine development was uncovered in the small-cell lung cancer model. The team demonstrated relevance to human lung cancer of the protein signatures identified on the basis of mouse models.