Highlights of This Issue

In cancer, increased caspase-3 activation linked to apoptotic cell death provides a mechanistic readout of drug response. Nguyen and colleagues establish that noninvasive positron emission tomography imaging with the caspase-3 binding probe [¹⁸F]ICMT-11 permits characterization of caspase-3 dynamics in vivo and the early assessment of apoptosis induced by both cytotoxic and mechanism-based drugs. As the development of noninvasive molecular imaging strategies to detect apoptosis continues to gain momentum, the authors demonstrate that this new imaging approach provides essential insights into the pharmacodynamics of anticancer agents and holds promise for predicting anticancer drug response in tumors.

Chondrosarcomas are notoriously resistant to chemotherapy, and novel therapeutic targets are needed. Zhang and colleagues show strong S6 phosphorylation in the majority of chondrosarcoma tumors and heterogeneous activation of receptor tyrosine kinases (RTK) in cell lines. Inhibition of phosphoinositide-3-kinase (PI3K) and mTOR, signaling proteins downstream of RTKs and upstream of S6, potently blocked growth of chondrosarcoma cells in vitro and in vivo. A subset of chondrosarcoma was identified to harbor NRAS mutations, and a corresponding cell line responded to MEK inhibition. These findings provide a rationale for clinical exploration of PI3K/mTOR and MAPK pathway inhibitors in this disease.

Effective cancer vaccines seem to require robust costimulatory immune activity spatiotemporally associated with the presentation of a broad array of patient-relevant cancer antigens. Conrad and colleagues developed a practical strategy to achieve this by administering a vaccine prepared through ex vivo infection of viable acute lymphocytic leukemia cells with attenuated yet highly immunogenic strains of engineered rhabdovirus. The potent immunotherapeutic [immunotherapy by leukemiaoncotropic virus (iLOV)] induced durable responses in vivo that required cytotoxic T cells to prevent the lethal progression of murine leukemia. This immune effect targeted only cells contained in the vaccine. iLOV represents a feasible approach to eliminate residual disease following remission induction.

Studies have identified the presence of bacteria within the tumors and mucin of patients with pseudomyxoma peritonei, an abdominal cancer originating from an appendiceal neoplasm. Semino-Mora and colleagues further demonstrate the important role of bacteria in pseudomyxoma peritonei disease. Antibiotic treatment significantly reduced bacterial density as well as β-catenin levels in the host cell cytoplasm, the cell nuclei, and mucin-associated cells of patients with peritoneal mucinous carcinomatosis. Furthermore, these patients exhibited a significant increase in β-catenin levels within host cell membranes. Both the reduced bacterial density and redistribution of β-catenin highlight the efficacy of antibiotics as a potential treatment for pseudomyxoma peritonei cancer.