Highlights of This Issue

Abstract

To explore the value of HER2 as a target in ovarian cancer, Faratian and colleagues evaluated the combination of the HER2-directed antibodies trastuzumab and pertuzumab in xenograft models. They found that the antibody combination was effective against high HER2-expressing tumors. Size, apoptosis, morphology, and estrogenregulated gene expression were modulated by the antibodies in a spatial and temporal manner. Further, trastuzumab increased ERα expression and enhanced sensitivity to letrozole. These results suggest that trastuzumab in combination with pertuzumab could be an effective treatment for high HER2-expressing ovarian cancers, and could also enhance sensitivity to endocrine therapy in ERα-positive ovarian cancer.Klotho is a transmembrane protein that can be shed and act as a circulating hormone. Here, Abramovitz and colleagues explored the expression and function of klotho in pancreatic cancer. They found that klotho expression was reduced in human pancreatic adenocarcinoma. Treatment with klotho or with KL1 internal repeat effectively slowed the growth of pancreatic cancer cells in vitro and in vivo and inhibited activation of the IGF-1 and FGF pathways. These findings indicate that klotho acts as a tumor suppressor and suggest that klotho may be used therapeutically or as a diagnostic marker in pancreatic cancer.In this issue, Kyte and colleagues report a trial evaluating combined therapy with temozolomide and the telomerase peptide vaccine GV1001 in advanced melanoma patients. They found that 18 of 23 subjects developed a telomerase-specific immune response, without notable toxicity. Patients developing longterm immunologic memory survived longer than those who rapidly lost immune response. Five patients developed partial tumor regression and overall survival (intention-totreat population) was extended compared with matched controls from a benchmark meta-analysis. These findings warrant further studies of GV1001/temozolomide treatment and support the concept of combining cancer vaccination with chemotherapy.Variable individual response to opioid therapy for cancer pain is an important problem in the clinical management of patients. In this issue, Galvan and colleagues carried out a genome-wide association study in 1,008 cancer patients undergoing opioid therapy. They identified eight genetic polymorphisms significantly associated with poor response to opioid therapy. Genes related to nerve impulse transmission rather than genes implicated in opioid pharmacology were tagged. These findings may represent a starting point to define therapeutic target(s) for countering poor pain relief, leading to improved quality of life for cancer patients.