Highlights of This Issue

This phase I multicenter study enrolled 42 patients with advanced cancer who were treated with a combination of the mTOR inhibitor temsirolimus with cixutumumab. The combination was well tolerated. Clinical benefits were observed in Ewing sarcoma and adrenocortical carcinoma. Pharmacodynamic data suggest that cixutumumab alone or combined with temsirolimus increased plasma insulin-like growth factor (IGF)-1 and IGF binding protein 3. Assessment via 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography combined with x-ray computed tomography showed the odds of achieving stable disease decreased by 58% (P = 0.1213) with a 1-unit increase in absolute change of standard uptake value from baseline to day 3.

Pancreatic cancers are resistant to most chemotherapeutic agents, and novel treatments are needed. Du and colleagues assessed the activity of an antimesothelin immunotoxin on pancreatic cancer cells and found that these cells are resistant to immunotoxin due to low levels of the proapoptotic protein Bak. Combining TRAIL or an anti-TRAIL receptor 2 antibody with immunotoxin caused synergistic cell death and reduced tumor volume in a xenograft mouse model. These data demonstrate that cancer cells with low BAK are resistant to immunotoxin treatment, and that combining immunotoxin with TRAIL or a TRAIL agonist antibody is an effective way to overcome such resistance.

Fas ligand (FasL)-844T/C polymorphism has a demonstrated association with tumor progression via immune escape. To explore the role of FasL haplotype on the outcome of resected non–small cell lung cancer (NSCLC), Sung and colleagues followed the survival and relapse of 385 NSCLC patients and determined their FasL-844 genotype. The FasL-844CC genotype was highly prevalent in patients with advanced tumors, who are prone to disease relapse. Additionally, patients with the FasL-844CC genotype had worse overall survival and relapse-free survival than did those with the FasL-844TT+TC genotype. Therefore, FasL-844 polymorphism evaluated by PCR restriction fragment length polymorphism may potentially predict disease relapse and prognosis in resected NSCLC.

Gemcitabine and doxorubicin (GEM/DOX) induced tumor suppressor sphingolipid C₁₈-ceramide generation and inhibited head and neck squamous cell carcinoma (HNSCC) tumor growth in preclinical studies. To evaluate the clinical efficacy and relevance of this strategy, Saddoughi and colleagues conducted a phase II trial in patients with recurrent HNSCC. In 17 patients, the median progression-free survival was 1.6 months [95% confidence interval (CI): 1.4, 4.2], with a median survival of 5.6 months (95% CI: 3.8, 18.2). C₁₈-ceramide elevation was observed in the serum of patients with response and stable disease, compared with progressive disease, suggesting that GEM/DOX-induced C₁₈-ceramide may be a novel serum biomarker for monitoring therapeutic response.