Highlights of This Issue

The work of Julien and colleagues represents the joint effort of a public/private consortium to characterize a new collection of patient-derived colorectal cancer models and evaluate drug sensitivity as a means to improve the standard of care. Maintenance of this repository of clinical features, even with the highly heterogeneous colorectal cancers, is allowing correlation with drug sensitivity and patient clinical history. Beyond the cetuximab sensitivity shown to be associated with KRAS status, this collection opens up new avenues to evaluate new targeted therapies or biomarkers in experimental phase II trials. Moreover, the occurrence of metastases emphasizes the value of patient-derived xenograft models as preclinical models relevant for translational research.

System xC⁻ plays an important role in growth and progression of cancer and glutathione-based drug resistance. The xCT subunit of system xC⁻ is stabilized by CD44 enabling better regulation of redox status. Baek and colleagues conducted an exploratory clinical trial with (4S)-4-(3-[¹⁸F]fluoropropyl)-L-glutamate ([¹⁸F]FSPG) in patients with non–small cell lung or breast cancer. The authors observed a high cancer detection rate of [¹⁸F]FSPG positron emission tomography (PET) and a correlation of [¹⁸F]FSPG uptake with the expression of the xCT subunit of system xC⁻ together with CD44. These findings suggest that [¹⁸F]FSPG PET can be used to assess xC⁻ transporter activity in cancer patients.

Mixed bacterial vaccine (MBV; Coley's toxins) is a historical, vaguely defined preparation of heat-inactivated Streptococcus pyogenes and Serratia marcescens used as nonspecific immunotherapy in the treatment of cancer. Karbach and colleagues revisit Coley's toxins with a phase I clinical trial examining the immune-modulatory and clinical effects of a new, biochemically well-defined and cGMP-compliant MBV preparation. The study shows safety and evidence of in vivo MBV effects through the production of inflammatory cytokines. These findings clearly indicate that a strong “danger signal” evokes measurable inflammatory immune responses that render MBV as a potent adjuvant treatment in combination with different strategies to treat cancer, including cancer vaccines.

Normal tissues are typically more sensitive to the size of daily doses (fractions) of radiotherapy than cancers are. However, recent evidence indicates that breast and prostate cancer are more sensitive to fraction size than is commonly assumed. Using human epidermis as a model, Somaiah and colleagues show that homologous recombination repair of radiation-induced DNA breaks is progressively activated during a course of radiotherapy. This finding correlates with the loss of fractionation sensitivity seen clinically. Adoption of homologous recombination, due to its high fidelity, may explain the loss of fractionation sensitivity in rapidly cycling normal and malignant tissues and suggests a potential approach to individualized treatment.