Highlights of This Issue

Abstract

Non–small cell lung carcinoma patients harboring activating EGF receptor (EGFR) mutations, e.g., exon 19 deletions, are best treated using tyrosine kinase inhibitors, such as erlotinib, rather than cytotoxic chemotherapy. However, identifying these patients is difficult because representative tumor samples are required and are often not available. In this study, Bahce and colleagues used radiolabeled erlotinib, [11C]erlotinib, and positron emission tomography to study tracer pharmacokinetic modeling in patients, and found that [11C]erlotinib showed higher volume of distribution, reflecting higher uptake in tumors with EGFR exon 19 deletions than in tumors without. [11C]erlotinib shows promise as an in vivo imaging biomarker to identify patients who may benefit from erlotinib treatment.Small cell lung cancer (SCLC) is a common form of lung cancer and is associated with very unsatisfactory survival rates. In this report, Wojtalla and colleagues show that the catalytic p110α isoform is overexpressed in a subset of primary SCLC samples. The growth of SCLC cells was impaired on targeting p110α using RNA interference or specific pharmacologic inhibitors. Inhibition of p110α also induced apoptosis by decreasing the expression levels of antiapoptotic Bcl-2 family proteins. Importantly, SCLC tumors treated with p110α inhibitors displayed reduced proliferation and enhanced apoptosis in vivo. Specific p110α inhibitors may in the future represent new drugs for SCLC.Sphingosine kinase 1 (SphK1) overactivation has been involved in resistance to anticancer targeted agents. Rosa and colleagues investigated its role in lack of response to the anti–EGF receptor (EGFR) monoclonal antibody cetuximab in colorectal cancer. In preclinical models with intrinsic or acquired resistance, SphK1 inhibition, through different approaches including the sphingosine-1-phosphate receptor antagonist fingolimod, restored sensitivity to cetuximab. A correlation between SphK1 expression and cetuximab response was found in metastatic colorectal cancer patients. These data support SphK1 inhibition as a part of novel therapeutic strategies to be tested for colorectal cancer patients resistant to anti-EGFR drugs.The azurophil granule protease cathepsin G is overexpressed in myeloid leukemia and plays an important role in leukemogenesis. Zhang and colleagues investigated the role of cathepsin G as a novel immunotherapeutic target in acute myeloid leukemia (AML). CG1 (FLLPTGAEA), a naturally processed HLA-A*0201 restricted peptide derived from cathepsin G, was identified on the surface of AML and was found to elicit potent immunity against primary AML blasts. In addition, an immune response targeting CG1 was detected in AML patients following allogeneic stem cell transplantation. Therefore, targeting cathepsin G using immunotherapeutic approaches seems promising in the treatment of AML.