Highlights of This Issue

AKT plays a central role in tumorigenesis and conveys resistance to standard therapies, implicating this kinase as a potential therapeutic target. To determine if inhibition of AKT by the selective small molecule inhibitor GSK690693 has therapeutic efficacy, Altomare and colleagues tested GSK690693 in three different genetically defined mouse models that develop spontaneous tumors with activated AKT. In each model tested, treatment with GSK690693 inhibited tumor formation and progression, irrespective of the mechanism of AKT activation involved. These results suggest that AKT inhibitors hold significant promise for treating human cancers dependent on AKT signaling.

Response to therapy for non–small cell lung cancer (NSCLC) may vary by histology. To explore whether microRNA expression profiles differ by histological subtypes and can predict survival for patients with NSCLC, Landi and colleagues analyzed microRNA expression in 165 adenocarcinoma (AD) and 125 squamous cell carcinoma (SQ) tissue samples using a custom microRNA-oligo array. Further, they replicated major findings in 125 additional samples by qRT-PCR. They found that microRNA expression profiles could differentiate AD from SQ, particularly in the early stages. Also, a 5-microRNA signature significantly predicted survival for SQ. These findings have the potential to lead to histology-based therapeutic approaches for lung cancer.

Glioblastoma (GBM) is a highly aggressive primary brain tumor in adults and five-year survival rates remain low. The recent identification of chemotherapy- and radiotherapy-resistant CD133- positive GBM stem cells may, in part, explain why conventional therapies are ineffective. Here, Ahmed and colleagues show that T cells from GBM patients can be modified with an HER2-specific chimeric antigen receptor to produce effector cells. They show that these HER2- specific T cells could kill autologous HER2-positive GBM cells (including CD133-positive GBM stem cells) and that they had potent antitumor activity in an orthotopic brain tumor model.

Outcome in follicular lymphoma is influenced by the microenvironment. The impact of the microenvironment may be multifactorial, but it remains unclear which specific immune cell subsets are of importance. Here, Wahlin and colleagues studied the lymphoma microenvironment by quantifying immunohistochemical staining on tissue microarrays of clinical lymphoma samples. They found that five subsets were associated with either good or poor prognosis, independently of each other and of clinical factors. These results provide a broad picture of the impact that various components of the lymphoma microenvironment have on outcome.